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at Department of Medical Biochemistry,Faculty of Medicine
shahid Beheshti of University of Medical Sciences,Iran
Mohsen Asadolahi, Abdolrahim Nikzamir, Majid Sirati-Sabet, Reza Mirfakhraie, Siamak Salami, Soroush Darbankhales, Kobra Saket-Kisomi, and Saina Ghadiany
International Journal of Cancer Management, ISSN: 25384422, eISSN: 2538497X, Published: March 2020 Kowsar Medical Institute
Ali J. Jahan‐Abad, Saeed Karima, Somayeh Shateri, Somayeh M. Baram, Shima Rajaei, Parastoo Morteza‐Zadeh, Maryam Borhani‐Haghighi, Ali‐Akbar Salari, Abdolrahim Nikzamir, and Ali Gorji
Neuropathology, ISSN: 09196544, eISSN: 14401789, Pages: 84-92, Published: 1 February 2020 Wiley
Experimental autoimmune encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS) is characterized by demyelination, infiltration of inflammatory cells into the nervous system and dysregulation of serum inflammatory cytokines. We investigated the correlation of serum cytokines and other inflammatory markers with the EAE pathogenesis. After EAE induction, the levels of different serum cytokine/inflammatory mediators were measured. Furthermore, motor functions, myelination, and lymphocyte infiltration in EAE mice were also assessed. Our results revealed that the serum concentrations of T-helper 1 (Th1) and Th17 cytokines, interleukin (IL)-6, IL-1β, IL-1α and prostaglandin E2 in EAE mice were significantly higher than controls. The ratios of pro- to anti-inflammatory cytokines were different between the EAE and the control group. A statistically significant positive correlation was found between the IL-6/IL-10 ratio and the EAE severity, demyelination rate, and lymphocyte infiltration in EAE mice. Results indicate that the profiles of serum pro- and anti-inflammatory cytokines might be useful as biomarkers for monitoring the pathological manifestation of EAE. Furthermore, evaluating the dynamic interplay of serum cytokine levels and the correlation with pathogenic mechanisms of EAE may provide diagnostic and therapeutic insights for MS and some other inflammatory disorders.
Nastaran Asri, , Mohammad Rostami-Nejad, Mohammad Barzegar, Abdolrahim Nikzamir, Mostafa Rezaei-Tavirani, Mohammadreza Razzaghi, Mohammad Reza Zali, , , , , , and
Iranian Biomedical Journal, ISSN: 1028852X, Pages: 140-147, Published: 2020 Armenian Green Publishing Co.
Celiac disease (CD) is a systemic immune-mediated disorder caused by the dietary gluten in individuals who are genetically susceptible to the disease. In fact, CD is a T cell-mediated immune disease in which gluten-derived peptides activate the lamina propria CD4+ Teff cells, and these T-cell subsets can cause the intestinal tissue damages. Also, there are additional subsets of CD4+ T cells with suppressor functions. These subsets express the master transcription factor, transcription factor forkhead box protein 3, and include Tr1 cells and CD4+CD25+ regulatory T cells (Tregs), which are the main population involved in maintaining the peripheral tolerance, preventing the autoimmune diseases and limiting the chronic inflammatory diseases such as CD. The suppressive function of Tregs is important to maintain the immune homeostasis. This paper examined the features and the basic mechanisms used by Tregs to mediate the suppression in CD.
Hamid Asadzadeh-Aghdaei, Farshad Okhovatian, Zahra Razzaghi, Mohammadhossein Heidari, Reza Vafaee, and Abdolrahim Nikzamir
Journal of Lasers in Medical Sciences, ISSN: 20089783, eISSN: 22286721, Pages: S59-S63, Published: 2019 International Society for Phytocosmetic Sciences
Introduction: Radiation therapy (RT) as a common method for cancer treatment could result in some side effects. The molecular investigation is one of the approaches that could assist in decrypting the molecular mechanisms of this incident. For this aim, protein-protein interaction (PPI) network analysis as a complementary study of the proteome is conducted to explore the RT effect on brain cancer after the early stage of exposure prior to the appearance of the skin lesion. Methods: Cytoscape 3.7.2 and its plug-ins were used to analyze the network of differential expression of proteins (DEPs) in the treatment condition, and the centrality and pathway enrichment was conducted by the use of NetworkAnalyzer and ClueGO+CluePedia. Results: A network of 15 DEPs indicated that 6 nodes were key players in the network stability and SERPINC1 and F5 were from the query proteins. The pathways of post-translational protein phosphorylation, platelet degranulation, and complement and coagulation cascades were the most highlighted ones for the central nodes that could be affected in RT. Conclusion: The central proteins of the network of early-stage treatments could have additional importance in the mechanisms of radiotherapy response prior to skin lesions. Introduced biomarkers can be used for the patients’ follow-up. These candidates are worth precise attention for this type of therapy after approving by validation studies.
Gastroenterology and Hepatology from Bed to Bench, ISSN: 20082258, eISSN: 20084234, Pages: 216-224, Published: 2018
Zeinab Barartabar, Abdolrahim Nikzamir, Majid Sirati-Sabet, Elham Aghamohammadi, Vahid Chaleshi, Mohammad Rostami Nejad, Hamid Asadzadeh-Aghdaei, and Mohammad Reza Zali
Przeglad Gastroenterologiczny, ISSN: 18955770, eISSN: 18974317, Pages: 293-298, Published: 2018 Termedia Sp. z.o.o.
Introduction Celiac disease (CD) is a chronic inflammatory intestinal disorder. Different immunological factors, including inflammatory cytokines, may play an important role in disease susceptibility. Aim To investigate the relationship between -174G/C and -572G/C gene polymorphisms and the serum level of interleukin 6 (IL-6) and susceptibility to CD in the Iranian population. Material and methods In this case-control study blood samples were collected of 105 patients with CD and 106 healthy subjects randomly in 2016 and evaluated by polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) method. A sequence was also used to confirm the results of both polymorphisms. The IL-6 concentration was measured using ELISA. Results The results showed a significant relationship between polymorphism -572G in CD patients when compared with control subjects by genotype (p = 0.001) and alleles (p = 0.022), respectively. There was no significant relationship between polymorphism 174G and frequency of genotype, but an association of this polymorphism with the frequency of alleles (p = 0.034), age (p = 0.001), and body mass index (p = 0.003) was seen. The serum level of interleukin-6 was significantly associated only with rs1800796 (p < 0.001). Conclusions The results confirm previous studies in different parts of the world and indicate that IL-6 (572G/C) polymorphism may play a role in susceptibility to CD in the Iranian population.
Padina Vaseghi Maghvan, Mostafa Rezaei-Tavirani, Hakimeh Zali, Abdolrahim Nikzamir, Saeed Abdi, Mahsa Khodadoostan and Hamid Asadzadeh-Aghdaei
Gastroenterology and Hepatology from Bed to Bench, ISSN: 20082258, eISSN: 20084234, Pages: 295-302, Published: 2017 Research Institute for Gastroenterology and Liver Diseases
Aim The aim of this study was to provide a biomarker panel for esophageal, gastric and colorectal cancers. It can help introducing some diagnostic biomarkers for these diseases. Background Gastrointestinal cancers (GICs) including esophageal, gastric and colorectal cancers are the most common cancers in the world which are usually diagnosed in the final stages and due to heterogeneity of these diseases, the treatments usually are not successful. For this reason, many studies have been conducted to discover predictive biomarkers. Methods In the present study, 507 genes related to esophageal, gastric and colon cancers were extracted.. The network was constructed by Cytoscape software (version 3.4.0). Then a main component of the network was analyzed considering centrality parameters including degree, betweenness, closeness and stress. Three clusters of the protein network accompanied with their seed nodes were determined by MCODE application in Cytoscape software. Furthermore, Gene Ontology (GO) analysis of the key genes in combination to the seed nodes was performed. Results The network of 17 common differential expressed genes in three esophageal, gastric and colon adenocarcinomas including 1730 nodes and 9188 edges were constructed. Eight crucial genes were determined. Three Clusters of the network were analyzed by GO analysis. Conclusion The analyses of common genes of the three cancers showed that there are some common crucial genes including TP53, EGFR, MYC, AKT1, CDKN2A, CCND1 and HSP90AA1 which are tightly related to gastrointestinal cancers and can be predictive biomarkers for these cancers.
Gastroenterology and Hepatology from Bed to Bench, ISSN: 20082258, eISSN: 20084234, Pages: 30-35, Published: 2016
Gastroenterology and Hepatology from Bed to Bench, ISSN: 20082258, eISSN: 20084234, Pages: 114-123, Published: 2016
Atousa Moradzadegan, Asad Vaisi-Raygani, Abdolrahim Nikzamir, and Zohreh Rahimi
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System, ISSN: 14703203, eISSN: 17528976, Pages: 672-680, Published: 1 September 2015 SAGE Publications
Hypothesis: Little is known about the concomitant presence of the angiotensin-converting enzyme (ACE) (rs4646994) D allele and vascular endothelial growth factor(VEGF) (+405G/C; rs2010963) G allele on the susceptibility of coronary artery disease (CAD). Here we examined the hypothesis that ACE-D and VEGF-G alleles act synergistically to increase the severity of CAD in patients with type II diabetes mellitus (T2DM). Materials and methods: The VEGF (rs2010963) and ACE (rs4646994) genotypes were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and PCR, respectively in 510 T2DM patients undergoing their first coronary angiography. Diabetic patients were classified as T2DM patients with and without CAD (control). Results: The crude odds ratio (OR) for the presence of CAD in ID+DD and D allele carriers were 1.98 (p=0.01) and 1.55 (p=0.001), respectively. Also, adjusted ORs in the presence of normolipidemia and the absence of history of hypertension for the risk of CAD in the either ACE(rs4646994) D allele or VGEF(rs2010963)-G alleles were 2.08 (p=0.004) and 1.75 (p=0.024), respectively. In addition, the concomitant presence of the ACE-D and VEGF-G alleles increased the risk of CAD 2.25-fold (p=0.043). Conclusion: Our results indicated that ACE(rs4646994)-D allele alone and in the presence of VEGF(rs2010963)-G allele can be an important independent risk factor for susceptibility of CAD in T2DM patients even after correcting for conventional risk factors in a population of Iran.
Mohammad Fathi, Abdol Rahim Nikzamir, Alireza Esteghamati, Manouchehr Nakhjavani, and Mir Saeed Yekaninejad
Iranian Red Crescent Medical Journal, ISSN: 20741804, eISSN: 20741812, Published: Dec-2015 Kowsar Medical Institute
BACKGROUND Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and vascular endothelial growth factor (VEGF) polymorphisms have been shown to associate with diabetic nephropathy (DN). OBJECTIVES We examined the hypothesis that ACE-D and VEGF-G alleles act synergistically in association with DN, in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS The VEGF (rs2010963) and ACE (rs4646994) genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 490 T2DM patients. Diabetic patients were classified as T2DM patients with and without albuminuria (control). The PCR and RFLP were used to detect the VEGF and ACE alleles. RESULTS A total of 255 consecutive patients with T2DM and microalbuminuria (Group A) and 235 patients with T2DM and normoalbuminuria (Group B) were included in the study. In univariate analysis, the groups were statistically similar for all variables, except for glycated hemoglobin (HbA1c) (P = 0.034), and the frequency of ACE (P = 0.015) and VEGF (P = 0.006) genotypes. Our study showed that the VEGF-G and ACE-D alleles are independently associated with the development of nephropathy. According to our data, the combination of these two risk factors had a significant synergistic effect on the risk of microalbuminuria development. CONCLUSIONS Our study indicated that ACE-D and VEGF-G alleles can be an independent risk factor for microalbominuria in T2DM patients.
Tanaffos, ISSN: 17350344, Pages: 51-54, Published: 2014
Iranian Journal of Pharmaceutical Sciences, ISSN: 17352444, Pages: 39-45, Published: 2014
Abdolrahim Nikzamir, Alireza Palangi, Alireza Kheirollaha, Hashemi Tabar, Alimohamad Malakaskar, Hajieh Shahbazian, and Mohammad Fathi
Iranian Red Crescent Medical Journal, ISSN: 20741804, Published: February 2014 Kowsar Medical Institute
BACKGROUND In diabetes mellitus because of the absence or insufficient sensitivity to insulin, glucose transporter protein in cell membrane, glucose transporter 4, is decreased. GLUT4 is the major glucose transporter in skeletal muscle and adipose tissue, which is under control of insulin. It remains, however, unclear whether cinnamaldehyde plays a regulatory role(s) or not. OBJECTIVES The objective of this study was to investigate the effects of cinnamaldehyde on GLUT4 gene expression. MATERIALS AND METHODS This study was an experimental trial. Tests were performed in triplicates. This study examined effects of cinnamaldehyde on Glut4 gene expression in C2C12 skeletal muscle cells by using Real Time PCR. C2C12 myoblasts were cultured in DMEM + 10 % FBS. After differentiation of myoblasts to myotubes, the cells were serum deprived for 5 hours and then treated with 10, 20, or 50 µM of cinnamaldehyde for 1 hour. RESULTS Our data revealed a significant increase in the expression of Glut4 in cinnamaldehyde treated cells. In addition, GLUT4 mRNA level was increased in a dose dependent manner. Analyses were performed using the SPSS 16 for Windows software. Differences between the groups were determined by one-way ANOVA. CONCLUSIONS These results demonstrate that cinnamaldehyde up regulates the expression of mouse skeletal muscle GLUT4 gene expression.
Behnaz Ahmadi, Abdolrahim Nikzamir, Seid Mohamadali Ghafari, Ghorban Mohamadzadeh, Mahmod Latifi, Ahmad Bafandeh, Mohammad Fathi, Mir Saeed Yekaninejad, and Mahfam Nikzamir
Molecular Biology Reports, ISSN: 03014851, eISSN: 15734978, Pages: 997-1001, Published: February 2014 Springer Science and Business Media LLC
Cyclooxygenases are key enzymes in conversion of arachidonic acid into prostaglandin H2. Cyclooxygenase-2 (COX-2) increases prostaglandins in neoplastic tissue. COX-2 has important roles in cell proliferation cancers, angiogenesis, and alzheimer. COX-2 is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Our main objective was to evaluated the association of polymorphism COX-2 with risk of breast cancer in khouzestan province, and the second objective of the study was to evaluate the association with biochemistry parameters. This study consisting of 150 patients with breast cancer and 120 normal DNA was extracted from the white blood cells. Polymorphism cox2 gene was detected by polymerase chain reaction according to the standard methods. The profile lipids and estrogen were measured in two groups by standard methods. Chi square analysis showed that there was no association between breast cancer risk and COX-2 −765G>C genotype and alleles. Also, no association were observed between −765G>C polymorphism and biochemistry parameters. A multiple logistic regression model with cox2 genotypes and LDL and HDL as covariates revealed that there is no significant association between cox2 genotypes and risk of breast cancer, but higher values of LDL and HDL significantly increase risk of breast cancer.
Archives of Iranian Medicine, ISSN: 10292977, eISSN: 17353947, Pages: 636-641, Published: November 2013
Javad Zavar Reza, Hossein Nahangi, Reza Mansouri, Ali Dehghani, Majid Mojarrad, Mohammad Fathi, Abdolrahim Nikzamir, and Mir Saeed Yekaninejad
Iranian Red Crescent Medical Journal, ISSN: 20741804, Pages: 554-559, Published: July 2013 Kowsar Medical Institute
BACKGROUND Macrophages derived foam cells are key factors in the maladaptive immune and inflammatory response. OBJECTIVES The study of the cholesterol homeostasis and the molecular factor involved in these cells is very important in understanding the process of atherosclerosis and the mechanisms that prevent its occurrence. MATERIALS AND METHODS This experimental study investigated the effects of c9, t11-Conjugated Linoleic Acid (c9, t11-CLA). Alpha Linolenic Acid (LA), and Eicosapentaenoic Acid (EPA) on the PPARα and ACAT1 mRNA expression by Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells. RESULTS Incubation of CLA, LA, EPA, and synthetic ligands did not prevent increasing the cellular total cholesterol (TC). Free cholesterol (FC) is increased by Sandoz58-035 (P = 0.024) and decreased by fatty acids and Wy14643 (Pirinixic acid) (P = 0.035). The pattern of distribution of %EC is similar to the EC pattern distribution. The ACAT1 mRNA expression was significantly increased by EPA (P = 0.009), but c9, t11- CLA, LA, Wy14643, and Sandoz58-035 had no significant effect on the mRNA level of ACAT1 expression compared to DMSO(Dimethyl sulfoxide). DISCUSSIONS In comparison to the control of Wy14643, Sandoz58-035, c9 and t11-CLA, EPA increased the PPARα mRNA levels (P = 0.024, P = 0.041, P = 0.043, and P = 0.004, respectively), even though, LA had no significant effect on the PPARα mRNA expression (P = 0.489). CONCLUSIONS Variations in the chemical structure of fatty acids can affect their physiological function.
Amir Abbas Hamedian, Alireza Esteghamati, Sina Noshad, Mohammad Mozafari, Hosein Moin-Tavakkoli, Manouchehr Nakhjavani, Touraj Mahmoudi, Mahfam Nikzamir, Reza Safary, and Abdolrahim Nikzamir
Molecular Biology Reports, ISSN: 03014851, eISSN: 15734978, Pages: 6213-6218, Published: May 2012 Springer Science and Business Media LLC
Vascular endothelial growth factor (VEGF) has long been recognized as a hypotensive mediator. Little is known regarding the contribution of polymorphisms in VEGF gene to essential hypertension (EH), however. We aimed to investigate the association between +405 VEGF C/G single nucleotide polymorphism (SNP) and occurrence of EH in a sample of patients with diabetes. A study population of 474 subjects with diabetes of which 45.6% (216) had EH was enrolled in this study. Interviews and physical examinations were performed in a clinical setting. Subjects were matched in baseline anthropometric and biochemical characteristics except for total cholesterol. Genotyping of +405 VEGF C/G (rs2010963) SNP was carried out using polymerase chain reaction–restriction fragment length polymorphism. The allelic distribution of the sample did not violate Hardy–Weinberg equilibrium. Subjects with EH had a higher frequency of G allele (P = 0.005). Additionally, those with EH had a significantly higher frequency of GG genotype (P = 0.015). In multivariate logistic regression models controlling for possible confounders, having GG against CC genotype was associated with an odds ratio of 2.51 (95% CI: 1.44–4.38; P = 0.001). Moreover, presence of each G allele was linked to a 1.58-fold increase in risk of having EH (95% CI: 1.200–2.086; P = 0.001). In conclusion, +405 VEGF C/G SNP is associated with EH in patients with diabetes, suggesting presence of G allele and GG or CG genotype confer susceptibility towards EH.
Touraj Mahmoudi, Maral Arkani, Khatoon Karimi, Akram Safaei, Fatemeh Rostami, Elham Arbabi, Mohamad Amin Pourhoseingholi, Seyed Reza Mohebbi, Abdolrahim Nikzamir, Sara Romani, Shohreh Almasi, Maryam Abbaszadeh, Mohammad Vafaei, and Mohammad Reza Zali
Molecular Biology Reports, ISSN: 03014851, eISSN: 15734978, Pages: 5277-5282, Published: May 2012 Springer Science and Business Media LLC
Vitamin D appears to have anti-tumor activities in the large bowel. Our aim was to investigate whether −4817 G>A (rs2238136) polymorphism located at 5′-untranslated region (5′-UTR) of the human vitamin D receptor (VDR) gene was associated with colorectal cancer (CRC) risk. We conducted a case–control study and VDR genotypes, determined by Bpu10I restriction endonuclease digestion of PCR-amplified DNA, were performed on 327 cases with CRC and 327 controls. The distribution of VDR −4817 G>A genotypes and alleles differed significantly between cases with CRC and controls even after adjustment for confounding factors such as age, BMI, sex, and smoking status. Individuals carrying the “AA” genotype had a 2.09-fold increased risk compared with those with “GG” genotype (P = 0.016, OR = 2.09, 95% CI = 1.15–3.78) and a 1.87-fold increased risk compared with those with “GG and GA” genotypes (P = 0.033, OR = 1.87, 95% CI = 1.05–3.33) for CRC. Furthermore, the VDR “A” allele was significantly overrepresented in cases with CRC than controls (P = 0.044; OR = 1.28, 95% CI = 1.01–1.63). Interestingly, the analysis of the SNP revealed that all these associations were stronger for women subjects than for all subjects combined. These data indicated for the first time a direct association between “AA” genotype of VDR gene −4817 G>A polymorphism and CRC, with a stronger association for female subjects. However, our findings remain to be confirmed in other populations.
Alireza Esteghamati, Nasrin Mansournia, Manouchehr Nakhjavani, Mohammad Ali Mansournia, Abdolrahim Nikzamir, and Mehrshad Abbasi
Molecular Biology Reports, ISSN: 03014851, eISSN: 15734978, Pages: 3791-3797, Published: April 2012 Springer Science and Business Media LLC
The relation of Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) with coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate the genetic influence of the adiponectin gene polymorphisms in the development of CAD among patients with Type 2 diabetes (T2D). The adiponectin genotypes were detected by polymerase chain reaction and restriction analysis (PCR-RFLP) in our patients. Two adiponectin gene (ADIPOQ) SNPs (i.e. SNPs +45T>G and +276G>T) were genotyped in 114 Type 2 diabetic subjects with CAD, and 127 Type 2 diabetic patients without CAD. Demographic and anthropometric data along with plasma biochemistry including lipids, glycemic indices, and adiponectin were collected. There was a significant difference in the distribution of genotypes of +45T/G and +276G/T between CAD and non-CAD individuals (P < 0.05). Based on our results SNP+276G>T is associated with decreased risk of CAD after adjustment for potential confounding factors [adjusted OR = 0.39 (95%CI: 0.22–0.68); P = 0.001]. Similar findings were not observed for the +45T>G SNP. Two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD [adjusted OR = 0.47 (95% CI: 0.32–0.94); P = 0.03 and adjusted OR = 0.33 (95% CI: 0.13–0.83); P = 0.02 respectively]. No significant difference was observed between HOMA-IR, BMI, waist circumference, history of hypertension, HbA1C, and lipid concentrations regarding the two SNPs. In conclusion, these findings suggest that T allele of +276G>T SNP is significantly associated with decreased risk of CAD in T2D Patients. Also Haplotype analysis showed that two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD.
Fariba Ranjzad, Touraj Mahmoudi, Atena Irani Shemirani, Aidin Mahban, Abdolrahim Nikzamir, Mohsen Vahedi, Mahnaz Ashrafi, and Hamid Gourabi
Molecular Biology Reports, ISSN: 03014851, eISSN: 15734978, Pages: 2313-2319, Published: March 2012 Springer Science and Business Media LLC
In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH), and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including 181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 “TT” genotype compared with “TG and GG” genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20–3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03–2.86). Furthermore, the ADIPOQ rs2241766 “T” allele was significantly overrepresented in women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18–2.70), and the difference remained significant after Bonferroni correction. Our findings suggest that the ADIPOQ rs2241766 “TT” genotype is a marker of increased PCOS susceptibility. This study also indicates for the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations.
Abdolrahim Nikzamir, Alireza Esteghamati, Amir Abbas Hammedian, and Touraj Mahmoudi
Molecular Biology Reports, ISSN: 03014851, eISSN: 15734978, Pages: 881-886, Published: February 2012 Springer Science and Business Media LLC
Observations on the association between the vascular endothelial growth factor (VEGF) gene polymorphism and nephropathy have been inconsistent, which might be due to ethnic and geographical variations. Furthermore, the relationship between +405 G/C polymorphism and albuminuria in the diabetic population has not been sufficiently studied. The aim of this study was to evaluate for the first time the possible association between +405 G/C polymorphism and albuminuria in an population from Tehran of Iran. A total of 255 consecutive patients with type 2 diabetes and microalbuminuria (Group A) and 235 patients with type 2 diabetes and normoalbuminuria (Group B) were included. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to detect the VEGF alleles. In univariate analysis, the groups were statistically similar in all variables except for HbA1c (8.53 ± 1.7 in Group A vs. 8.2 ± 1.73 in Group B; P = 0.034), 24-h urinary albumin (201.33 ± 84.8 in Group A vs. 22.88 ± 3.5 in Group B; P < 0.001), and the frequency of GG genotype (31% in Group A vs. 18.7% in Group B; P = 0.006). The GG genotype was the independent predictor of albuminuria [P = 0.014, OR = 1.771, 95% confidence interval (CI) = 1.124–2.790]. Our study showed that the G allele was not associated with albuminuria, but the GG genotype in the VEGF gene is independently associated with development of nephropathy in the our diabetic population.
Fariba Ranjzad, Aidin Mahban, Atena Irani Shemirani, Touraj Mahmoudi, Mohsen Vahedi, Abdolrahim Nikzamir, and Mohammad Reza Zali
Journal of Assisted Reproduction and Genetics, ISSN: 10580468, eISSN: 15737330, Pages: 225-232, Published: March 2011 Springer Science and Business Media LLC
PurposeThe purpose of this study was to evaluate the associations between polymorphisms in vitamin D receptor (VDR), parathyroid hormone (PTH), calcium sensing receptor (CASR), insulin receptor (INSR), and adiponectin (ADIPOQ) genes and biochemical characteristics of women with polycystic ovary syndrome (PCOS).MethodsSerum levels of LH, FSH, estradiol, testosterone, prolactin, SHBG, glucose, IGF-1, IGFBP-1, calcium, phosphorus, PTH, 25(OH)D, and 1,25(OH)2 D were measured in 56 women with PCOS. Furthermore, genotyping five, one, one, two, and two polymorphisms of the VDR, PTH, CASR, INSR, and ADIPOQ genes, respectively, were performed.ResultsThe VDR TaqI “CC” genotype was associated with elevated serum levels of LH (p = 0.011). There were significant associations between decreased levels of SHBG and both VDR BsmI “GG” (p = 0.009) and ADIPOQ BsmI “CC” (p = 0.016) genotypes. Furthermore, patients with CaSR Hin1I “TG” genotype showed higher HoMA-IR (p = 0.008). All these associations remained significant after Bonferroni correction. In addition, phosphorus correlated negatively with estradiol (r = −0.298, P = 0.026) and positively with glucose (r = 0.287, P = 0.032).ConclusionsThese data indicated for the first time that it is possible that the VDR and CASR gene variants through their effects on LH and SHBG levels, and insulin resistance are involved in pathogenesis of PCOS.
Mostafa Feghhi, Abdolrahim Nikzamir, Alireza Esteghamati, Touraj Mahmoudi, and Mir Saeed Yekaninejad
Translational Research, ISSN: 19315244, eISSN: 18781810, Volume: 158, Pages: 85-91, Published: August 2011 Elsevier BV
The role of the vascular endothelial growth factor (VEGF) gene polymorphism in proliferative diabetic retinopathy (PDR) is controversial. VEGF seems to play a central role in mediating microvascular pathology in proliferative diabetic retinopathy (PDR). Recently, a +405 G/C VEGF polymorphism was shown to be associated with PDR. The aim of the current study was to evaluate whether the VEGF gene polymorphism is an independent risk factor for severity of diabetic retinopathy in an Iranian adult population. A total of 119 consecutive patients with PDR (group A) and 279 patients with nonproliferative diabetic retinopathy NPDR (group B) were studied. Patients were recruited from the eye clinic of Ahvaz Jondi Shapour University of Medical Sciences between January 2007 and April 2009. After extraction of genomic DNA, genotyping of the +405 G/C polymorphism of the VEGF gene was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Demographic, anthropometric, and plasma biochemistry data were recorded. In univariate analysis, the groups were statistically similar in all variables except for hemoglobin A1c (HbA1c) and +405 G/C polymorphism. The distribution of the GC genotype was significantly different in patients with PDR compared with NPDR. In a multivariate logistic regression analysis (using sex and body mass index as clinically significant variables and HbA1c and genotype as statistically significant variables) was then used to determine independent associations and adjusted odds ratios (ORs), the GG genotype (compared with the CC genotype) was an independent predictor of PDR [OR = 1.87, 95% confidence interval (CI) = 1.034-3.383 P = 0.039]. The HbA1c was more common in the PDR group (P = 0.004); in a multivariate regression, the association remained significant (OR = 1.194, 95% CI = 1.056-1.350, P = 0.005). These findings suggest that the VEGF +405 GG polymorphism might be associated with the risk of proliferative diabetic retinopathy in an Iranian population.
Manouchehr Nakhjavani, Alireza Esteghamati, Azam M. Tarafdari, Abdolrahim Nikzamir, Haleh Ashraf, and Mehrshad Abbasi
Gynecological Endocrinology, ISSN: 09513590, eISSN: 14730766, Pages: 14-19, Published: January 2011 Informa UK Limited
OBJECTIVES The objective of this study was to assess the association of serum leptin levels with insulin resistance (IR), metabolic syndrome (MetS), lipid levels, and glucose control in an Iranian type 2 diabetic population. FINDINGS In this cross-sectional analysis, 132 type 2 diabetic patients (79 women) and 71 healthy non-diabetic and non-hypertensive individuals (40 women; as control subjects) were included. Homeostasis model assessment (HOMA) of insulin values ≥ 1.8 for females and 1.7 for males was regarded as the cut-point of IR. MetS was defined according to updated 2005 NCEP ATP III criteria. The leptin correlated with HOMA-IR values without adjustment (r = 0.24; p < 0.005) and with adjustment for sex and diabetes (r = 0.44; p < 0.005). Sex had significant effect on the BMI adjusted association of HOMA-IR (quintiles) and leptin (df = 4 F(12.7) = 3.5; p = 0.011). In diabetic women (but not men), leptin levels were different between those with and without IR (27.3 ± 1.9 vs. 18.2 ± 3.3; p < 0.05). BMI adjusted leptin values were different between subjects with and without MetS (22.2 ± 1.7 vs.14.8 ± 1.2; p < 0.001). No association was noticed between BMI-adjusted leptin with glycated hemoglobin or blood lipid levels. CONCLUSIONS In this study, plasma leptin concentration correlated with IR independent of the effect of obesity in female but not male diabetic subjects.
J.Z. Reza, A. Nikzamir, M. Doosti, and M.S. Pour
Journal of Biological Sciences, ISSN: 17273048, eISSN: 18125719, Pages: 785-789, Published: 2010 Science Alert
Abdolrahim Nikzamir, Armin Rashidi, Alireza Esteghamati, Manouchehr Nakhjavani, Taghi Golmohammadi, and Omid Khalilzadeh
Ophthalmic Genetics, ISSN: 13816810, eISSN: 17445094, Pages: 108-113, Published: September 2010 Informa UK Limited
BACKGROUND The role of genetic factors in diabetic retinopathy (DR) is unclear. We investigated the relationship between DR and an insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene in Iranian patients with type 2 diabetes without overt nephropathy. METHODS A total of 178 consecutive type 2 diabetic patients with DR (Group A) and 206 type 2 diabetic patients without DR (Group B) were studied. The following variables were determined: age, sex, body mass index, diabetes duration, medications used, history of coronary artery disease and its complications, blood pressure (systolic and diastolic), fasting plasma glucose, hemoglobin A1c, total cholesterol, low- and high-density lipoproteins, triglycerides, plasma creatinine, and 24-h urine albumin excretion. RESULTS The groups were statistically similar in all variables except diabetes duration (P = 0.037), ACE activity (P < 0.001), and ACE genotype (P = 0.008). The DD genotype was significantly more common in Group A (32.6% versus 19.2% in Group B; P = 0.009). In multivariate regression analysis, the ID genotype (compared to the II genotype) was an independent predictor of DR (OR = 1.831, 95% CI = 1.074-3.124; P = 0.026). CONCLUSIONS The D allele of the ACE gene is independently associated with DR in Iranian type 2 diabetic patients.
Mahmoud Doosti, Mahdi Najafi, Javad Zavar Reza, and Abdolrahim Nikzamir
Translational Research, ISSN: 19315244, Volume: 155, Pages: 185-190, Published: April 2010 Elsevier BV
ATP-binding cassette transporter A1 (ABCA1) plays a pivotal role in intracellular cholesterol removal and exerts a protective effect against atherosclerosis. The role of genetic factors in susceptibility to coronary artery disease (CAD) is not clear. The aim of this study was to evaluate for the first time the possible association between R219K gene polymorphism and coronary artery disease in an Iranian adult population. A total of 207 consecutive patients with CAD (group A) and 94 patients without CAD (group B) were studied. We determined the presence of the R219K variant in the ABCA1 gene by polymerase chain reaction (PCR) and restriction analysis in 301 patients with and without CAD. The distribution of genotypes among the 2 groups was significantly different (P=0.009). In univariate analysis (with genotype AA as reference), the GG genotype was associated with a significantly increased risk of CAD (P=0.002; odds ratio [OR]=2.761; 95% confidence interval [CI]=1.418-5.374), but the GA genotype did not show a significant association (P=0.234) (data not shown). A multivariate logistic regression analysis (using sex as clinically significant variable, and using age, diabetes mellitus, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein [HDL], smoking, body mass index [BMI], and genotype as statistically significant variables) was used to determine independent associations and adjusted ORs. The GG genotype (compared with the AA genotype) was an independent predictor of CAD (OR=2.856, 95% CI=1.307-6.241; P=0.009), followed by BMI (P=0.034; OR=1.100; 95% CI=1.007-1.200). The GG genotype in the ABCA1 gene is independently associated with CAD in Iranian patients.
Abdolrahim Nikzamir, Alireza Esteghamati, Mostafa Feghhi, Manouchehr Nakhjavani, Armin Rashidi, and Javad Zavar Reza
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System, ISSN: 14703203, Pages: 109-114, Published: 2009 SAGE Publications
Introduction. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been shown to be associated with a number of complications of type 2 diabetes. Results on the development and progression of albuminuria, however, have remained controversial, with ethnic differences being a potential reason.The present study is the first report to examine Iranian patients. Methods. Patients (322; 162 males) with type 2 diabetes were categorised in this cross-sectional study into the following groups: normoalbuminuria (n=145), microalbuminuria (n=129) and macroalbuminuria (n=48).ACE gen I/D polymorphism genotypes were determined using the polymerase chain reaction method. Results. The distribution of ACE genotypes was significantly different among the groups (p<0.001), with the II genotype decreasing and the DD genotype increasing in frequency with increasing severity of albuminuria. Multivariate regression analysis showed that the ACE genotype did not change the odds of having microalbuminuria versus normoalbuminuria, while the D allele independently increased the odds of having macroalbuminuria versus microalbuminuria approximately threefold (p<0.01). Conclusions. In Iranian patients with type 2 diabetes, the D allele is associated with progression, but not development, of albuminuria.
Manouchehr Nakhjavani, Alireza Esteghamati, Firouzeh Asgarani, Omid Khalilzadeh, Abdolrahim Nikzamir, and Reza Safari
Translational Research, ISSN: 19315244, Volume: 153, Pages: 86-90, Published: February 2009 Elsevier BV
Recent in vitro evidence suggests that oxidized low-density lipoprotein (ox-LDL) stimulates the expression of transforming growth factor-beta (TGF-beta) by human glomerular epithelial cells. An elevated level of TGF-beta, which is a multifunctional growth cytokine, is also reported in diabetic patients. This study aimed to determine the association between ox-LDL and TGF-beta in healthy and type 2 diabetic participants. A total of 80 type 2 diabetic patients, who were referred to the outpatient diabetes clinic of a university general hospital, and 80 healthy controls matched for sex, age, and body mass index (BMI) were recruited. Fasting blood samples were obtained, and fasting plasma glucose, cholesterol, high-density lipoprotein-cholesterol (HDL-c), LDL-cholesterol, triglycerides, creatinine, HbA1C, ox-LDL, and TGF-beta were measured. Ox-LDL and TGF-beta were significantly greater in diabetic patients than healthy controls (72.66 +/- 3.11, 46.02 +/- 1.64, P < 0.001 and 4.75 +/- 0.43, 2.06 +/- 0.31, P < 0.001, respectively). Ox-LDL was significantly correlated to TGF-beta in diabetic patients (r = 0.318, P = 0.004). This significant association was not observed in healthy controls (r = 0.148, P = 0.191). In multivariate linear regression analysis after adjustment for age, sex, BMI, and creatinine, ox-LDL was a significant independent predictor of TGF-beta (beta = 0.308, P = 0.007). In conclusion, this study demonstrated that ox-LDL is significantly correlated to TGF-beta in type 2 diabetic patients.
Pakistan Journal of Medical Sciences, ISSN: 1682024X, Pages: 712-718, Published: October 2008
Acta Medica Iranica, ISSN: 00446025, eISSN: 00446025, Pages: 277-282, Published: 2008
Mostafa Feghhi, Abdolrahim Nikzamir, Alireza Esteghamati, Fereidoon Farahi, Manouchehr Nakhjavani, and Armin Rashidi
Diabetes Research and Clinical Practice, ISSN: 01688227, Published: September 2008 Elsevier BV
A total of 136 type 2 diabetic patients with nonproliferative and 94 patients with proliferative diabetic retinopathy (PDR) without nephropathy were studied. The DD genotype of the angiotensin-converting enzyme polymorphism was more common in the PDR group (P<0.001). In multivariate regression, the association remained significant (OR=3.516).
A. Nikzamir, M. Nakhjavani, A. Esteghamati, and A. Rashidi
Nephrology Dialysis Transplantation, ISSN: 09310509, eISSN: 14602385, Pages: 1274-1277, Published: April 2008 Oxford University Press (OUP)
The activity of the renin-angiotensin-aldosterone system (RAAS) plays an important role in the development and progression of diabetic nephropathy. However, the effect of angiotensin-converting enzyme (ACE) inhibition on the RAAS appears to be modulated by a number of factors including the I/D polymorphism of the ACE genotype. In this study, we attempted to find independent correlates of ACE activity in 121 macroalbuminuric type 2 diabetic Iranian patients under chronic ACE inhibition. Both univariate and multivariate analyses were used. The presence of the D allele was independently associated with significantly higher levels of ACE activity (with the II genotype as reference, P < 0.001, B = 27.3, 95% CI = 17.6-37.1), and this association was not eliminated by potentially confounding variables. In conclusion, the D allele is a significant independent correlate of ACE activity in macroalbuminuric type 2 diabetic Iranian patients under long-term ACE inhibition.
Archives of Iranian Medicine, ISSN: 10292977, Pages: 3-9, Published: January 2008
M. Nakhjavani, F. Esfahanian, A. Jahanshahi, A. Esteghamati, A. R. Nikzamir, A. Rashidi, and M. Zahraei
Nephrology Dialysis Transplantation, ISSN: 09310509, eISSN: 14602385, Pages: 2549-2553, Published: September 2007 Oxford University Press (OUP)
BACKGROUND Observations on the association between the ACE gene polymorphism and hypertension have been inconsistent, which might be due to ethnic and geographical variations. Moreover, the relationship between insertion/deletion (I/D) polymorphism and hypertension in the diabetic population has not been sufficiently studied. The aim of this study was to evaluate for the first time the possible association between I/D polymorphism and hypertension in an Iranian diabetic adult population. METHODS A total of 82 consecutive patients with type 2 diabetes and hypertension (Group A) and 87 patients with type 2 diabetes but without hypertension (Group B) were included. Patients who had a history of hypertension before the onset of diabetes and those with findings suggesting secondary hypertension were excluded. The following variables were determined for each patient: age, sex, body mass index (BMI), diabetes duration and the drugs used, history of coronary artery disease and its complications, blood pressure (systolic and diastolic), fasting blood sugar (FBS), haemoglobin A1c (HbA1c), total cholesterol (Chol), low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides (TG), plasma creatinine (Crt) and 24 h urine albumin excretion. Polymerase chain reaction (PCR) was used to detect the I/D alleles. Univariate (chi-squared and t-test) and multivariate (multivariate binary logistic regression with adjusted odds ratios) analyses were applied to determine the association between I/D polymorphism (with genotype II as reference) and hypertension. P<0.05 was considered statistically significant. RESULTS In univariate analysis, the groups were statistically similar in all variables except for diabetes duration (156.05+/-73.54 months in Group A vs 121.74+/-65.53 months in Group B; P=0.002), Crt (1.04+/-0.25 mg/dl in Group A vs 0.93+/-0.23 mg/dl in Group B; P=0.003), albuminuria (486.25+/-484.60 mg/d in Group A vs 316.50+/-459.56 mg/d in Group B; P=0.021) and the frequency of DD genotype (27 cases in Group A vs 11 cases in Group B; P=0.026). Multivariate logistic regression (using age, sex and BMI as clinically significant variables and diabetes duration, Crt, albuminuria and genotype as statistically significant variables) was then used to determine independent associations and adjusted odds ratios (OR). The DD genotype was the strongest independent predictor of hypertension [P=0.029, OR=3.122, 95% confidence interval (CI)=1.127-8.647], followed by log (albuminuria) (P=0.042, OR=1.183, 95% CI=1.006-1.391). Considering albuminuria as a categorical variable did not change the results significantly. CONCLUSION The DD polymorphism in the ACE gene is independently associated with hypertension in the diabetic population.
Iranian Journal of Immunology, ISSN: 17351383, eISSN: 1735367X, Pages: 23-29, Published: 2006
Iranian Journal of Public Health, ISSN: 22516085, eISSN: 22516093, Pages: 14-21, Published: 2006