VALERIA PONCE DE LEON SUAREZ

RESEARCH, TEACHING, or OTHER INTERESTS

Multidisciplinary, Biochemistry, Genetics and Molecular Biology, Molecular Medicine, Cancer Research

Scopus Publications

Association of Polymorphisms in Estrogen Receptor Genes (ESR1 and ESR2) with Osteoporosis and Fracture-Involvement of Comorbidities and Epistasis
M. Davidnia García-Rojas, Grecia Palma-Cordero, Celeste O. Martínez-Ramírez, Valeria Ponce de León-Suárez, Margarita Valdés-Flores, Clementina Castro-Hernández, Julieta Rubio-Lightbourn, Edgar Hernández-Zamora, Elba Reyes-Maldonado, Rafael Velázquez-Cruz,et al.
Mary Ann Liebert Inc
Single-nucleotide polymorphisms (SNPs) in the ESR1/ESR2 genes play a role in osteoporosis (OP). Our objective was to determine associations of polymorphisms in ESR genes with OP and fracture, SNP-SNP interactions, and involvement of comorbidities. We analyzed 170 Mexican osteoporotic women (FNOP), 173 with hip fracture (HFx), and 210 controls. The SNPs, ESR1 rs2234693CC, rs851982CC and rs1999805AA, were associated with reduced OP risk (odds ratios [ORs] = 0.35, 0.40 and 0.32, respectively; p < 0.05); rs2234693CC was associated with reduced fracture risk (OR = 0.24; p < 0.05). The obese/overweight carriers of rs9340799GG had a lower OP (OR = 0.15, p = 0.016) and fracture (OR = 0.12, p = 0.0057) risk. The rs9479055AA and rs3020404AA hypertensive carriers had a higher OP risk (OR = 5.96, p = 0.032; and OR = 5.29, p = 0.02, respectively). In addition, rs3020404AA had a higher risk of fracture (OR = 4.90, p = 0.045). The rs2228480GG hypertensive carriers had a higher risk of fracture (OR = 6.22, p = 0.0038). We found a synergic relation between the ESR1 rs3020331 and rs1999805 in femoral neck OP and HFx. The rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms are associated with a high risk forming a haplotype. The epistasis analysis suggests the contribution of both genes (ESR1/ESR2) to the risk of OP and fracture. Epistasis and involvement of obesity and hypertension lead to a significant modification of the risk.


High risk of lumbar spine osteoporosis with the RANK rs3018362 polymorphism
Leonora Casas-Avila, Esteban Cruz-Arenas, Valeria Ponce-de-León-Suárez, Guadalupe Sánchez-Bringas, Brenda Olivares-Bañuelos, Tatiana Chávez-Heres, and Margarita Valdés-Flores
Informa UK Limited
Abstract Osteoporosis is characterized by reduced bone mineral density (BMD) and quality, increasing the risk of fractures. A large number of genes involved in bone metabolism have been implicated in the genesis of osteoporosis; these include RANK and RANKL. Polymorphisms of these genes have been implicated in osteoporosis. The aim of this study was to determine the association of the RANK rs3018362 and RANKL rs12585014 polymorphisms with risk of osteoporosis. Four hundred Mexican women aged 40 years old or above were genotyped by real-time PCR and several demographic and risk factors were explored. The GA and AA genotypes of the rs3018362 polymorphism were associated with a high risk of osteoporosis in the dominant model (p=.0062; OR = 2.16, 95% CI: 1.24–3.78). In summary, the rs3018362 polymorphism in the RANK gene seems to be associated with osteoporosis of the lumbar spine while the RANKL rs12585014 is not, although more studies are needed to confirm these results.


Association of the Promoter Methylation and the rs12917 Polymorphism of MGMT with Formation of DNA Bulky Adducts and the Risk of Lung Cancer in Mexican Mestizo Population
Ollin Celeste Martínez-Ramírez, Rebeca Pérez-Morales, Clementina Castro-Hernández, Maria Eugenia Gonsebatt, Leonora Casas-Ávila, Margarita Valdés-Flores, Pavel Petrosyan, Valeria Ponce de León-Suárez, and Julieta Rubio
Mary Ann Liebert Inc
O6-Methylguanine-DNA methyltransferase (MGMT) is an enzyme that repairs the DNA damage caused by the tobacco habit, and low activity of this enzyme has been associated with a risk of lung cancer (LC). Our objective was to determine the association of the promoter methylation and the rs12917 polymorphism of MGMT with formation of DNA bulky adducts and the risk of LC in the Mexican Mestizo population. In this study are included 431 subjects. High-resolution melting analysis was used to determine the polymorphism MGMT rs12917 and methylation levels. DNA bulky adducts were determined by 32P-postlabeling. Our results showed that MGMT rs12917 and higher levels of methylation in the MGMT promoter are associated with the risk of LC. The levels of adducts are related with the phe/phe genotype and, only in the cases group, with the hypermethylation (>50%) of MGMT; however, this last association was not statistically significant.


The RANKL rs12585014 polymorphism is associated with age at menarche in postmenopausal women with hip fracture
Leonora Casas-Avila, Valeria Ponce de León-Suárez, Rosenda I. Peñaloza-Espinosa, Ricardo M. Cerda-Flores, Alin Pérez-Ríos, O. Celeste Martínez-Ramírez, Julieta Rubio-Lightbourn, Clementina Castro-Hernández, and Margarita Valdés-Flores
Informa UK Limited
Abstract The RANK/RANKL/OPG signaling is important in the regulation of bone turnover. The aim of the present work was to analyze the rs3018362 and rs12585014 polymorphisms in the RANK and RANKL genes, as well as risk factors in postmenopausal women. Women with hip fracture, with femoral neck osteoporosis and controls (n = 646) were recruited. From these, 303 women who fulfill the inclusion criteria were genotyped using real-time PCR with TaqMan probes. There were no associations of the rs3018362 and rs12585014 with osteoporosis or fracture. When women were divided by age at menarche, the rs12585014 GG genotype was strongly associated with age at menarche >13 years [p = .00774, OR = 6.429 (1.907–21.103)] in women with hip fracture. Significant differences in risk factors such as body mass index, age at menopause, use of estrogens, the presence of hypertension, and diabetes mellitus were found. Carrying the GG genotype of rs12585014 entails a higher risk of having menarche later (>13 years), which could involves a greater risk of fractures. The rs3018362 and rs12585014 do not seem to be associated with hip osteoporosis or hip fracture in Mexican women.


Two novel mutations in the GAN gene causing giant axonal neuropathy
Monica Irad Normendez-Martínez, Lucero Monterde-Cruz, Roberto Martínez, Magdalena Marquez-Harper, Nayelli Esquitin-Garduño, Margarita Valdes-Flores, Leonora Casas-Avila, Valeria Ponce de Leon-Suarez, Viktor Javier Romero-Díaz, and Alberto Hidalgo-Bravo
Springer Science and Business Media LLC



Association of the IL6 rs1800796, but not of the IL6 rs1800795, IL6R rs4845617 and rs2228145 polymorphisms with hip fracture in elderly Mexican women
Valeria Ponce de León-Suárez, Margarita Valdés-Flores, Antonio Miranda-Duarte, Esperanza Ramírez-Pérez, Alin Pérez-Ríos, Blanca Barredo-Prieto, Alberto Hidalgo-Bravo, and Leonora Casas-Avila
Springer Science and Business Media LLC



Association of a (TTTA)n microsatellite and a TCT del/ins polymorphisms in the aromatase gene (CYP19) with hip fracture risk in Mexican postmenopausal women
Leonora Casas-Avila, Margarita Valdés-Flores, Antonio Miranda-Duarte, Valeria Ponce de León-Suárez, Clementina Castro-Hernández, Julieta Rubio-Lightbourn, and Alberto Hidalgo-Bravo
Informa UK Limited
Abstract A (TTTA)n polymorphism in the aromatase gene has been studied in relation to bone mineral density (BMD). The low number of TTTA repeats has been associated with low BMD and fracture risk. The aim of this study was to search for associations of TTTA copy number with hip fracture and lumbar spine osteoporosis in Mexican peri and postmenopausal women. The allele with seven repeats was present in the two reported versions, with or without a TCT deletion upstream of the microsatellite (A1 and A2, respectively). After adjustment by confounders, the A1 allele and the A1A1 genotype were significantly associated with an elevated risk of fracture (p = 0.034, OR = 3.2 [95% CI, 1.09–9.41] and p = 0.019, OR = 2.26 [95% CI, 1.14–4.49], respectively) and the A2 allele was associated with protection of hip fracture (p = 0.04, OR = 0.48, [95% CI, 0.22–1.05]) as the A2A2 genotype (p = 0.048, OR = 0.29 [95% CI, 0.06–1.16]). The analysis allowed us to defining the usefulness of the (TTTA)n polymorphism in the aromatase gene as an indicator of hip fracture risk in Mexican population.


Genetic aspects of osteoporosis




Changes in P-glycoprotein activity are mediated by the growth of a tumour cell line as multicellular spheroids
Ponce de León Valeria and Barrera-Rodríguez Raúl
Springer Science and Business Media LLC
Abstract Background Expression of P-glycoprotein (P-gp), the multidrug resistance (MDR) 1 gene product, can lead to multidrug resistance in tumours. However, the physiological role of P-gp in tumours growing as multicellular spheroids is not well understood. Recent evidence suggests that P-gp activity may be modulated by cellular components such as membrane proteins, membrane-anchoring proteins or membrane-lipid composition. Since, multicellular spheroids studies have evidenced alterations in numerous cellular components, including those related to the plasma membrane function, result plausible that some of these changes might modulate P-gp function and be responsible for the acquisition of multicellular drug resistance. In the present study, we asked if a human lung cancer cell line (INER-51) grown as multicellular spheroids can modify the P-gp activity to decrease the levels of doxorubicin (DXR) retained and increase their drug resistance. Results Our results showed that INER-51 spheroids retain 3-folds lower doxorubicin than the same cells as monolayers however; differences in retention were not observed when the P-gp substrate Rho-123 was used. Interestingly, neither the use of the P-gp-modulating agent cyclosporin-A (Cs-A) nor a decrease in ATP-pools were able to increase DXR retention in the multicellular spheroids. Only the lack of P-gp expression throughout the pharmacological selection of a P-gp negative (P-gpneg) mutant clone (PSC-1) derived from INER-51 cells, allow increase of DXR retention in spheroids. Conclusion Thus, multicellular arrangement appears to alter the P-gp activity to maintain lower levels of DXR. However, the non expression of P-gp by cells forming multicellular spheroids has only a minor impact in the resistance to chemotherapeutic agents.