Maria Luisa Mansego
@navarrabiomed.es
posdoctoral researcher
Navarrabiomed
Scopus Publications
Scopus Publications
Ricardo Usategui-Martín, José Luis Pérez-Castrillón, María L. Mansego, Francisco Lara-Hernández, Iris Manzano, Laisa Briongos, Jesica Abadía-Otero, Javier Martín-Vallejo, Ana B. García-García, Juan Carlos Martín-Escudero,et al.
Elsevier BV
Marcos Garcia-Lacarte, Maria L. Mansego, M. Angeles Zulet, J. Alfredo Martinez, and Fermin I. Milagro
MDPI AG
The aim of the present investigation was to identify putative miRNAs involved in the response to weight loss. Reverse-transcribed RNA isolated from white blood cells (WBCs) of a subpopulation from the Reduction of the Metabolic Syndrome in Navarra-Spain (RESMENA-S) study (low-responders (LR) and high-responders (HR)) was hybridized in a gene expression microarray. Moreover, miRNAs were sequenced by miRNA-Seq. It was found that miR-548q and miR-1185-1 were overexpressed in HR, both in the microarray and in the miRNA-Seq. A bioinformatic prediction of putative target genes of the selected miRNAs found that GSK3B, a putative target for miR-548q and miR-1185-1, was downregulated in HR. Particular 3′-UTR binding regions of GSK3B were cloned downstream of the firefly luciferase gene. HEK-293T cells were co-transfected with either 0.25 μg of empty pmiR-GLO or pmiR-GLO-548q-3′-UTR/pmiR-GLO-1185-1-3′-UTR, and 7.5 pmol of miR-548q/miR-1185-1 mimics, demonstrating that miR-1185-1 bound to the 3′-UTR region of GSK3B. THP-1 cells were transfected with either 20/40 nM of miR-548q/miR-1185-1 mimics, evidencing that miR-1185-1inhibited the expression of the gene when transfected at doses of 20/40 nM, whereas miR-548q inhibited GSK3B expression at a dose of 40 nM. As a conclusion, miR-548q and miR-1185-1 levels in WBCs are biomarkers of response to weight-loss diets and could be involved in the regulation of the proinflammatory gene GSK3B.
Ana Arpón, Fermín I. Milagro, Omar Ramos-Lopez, M. Luisa Mansego, José Luis Santos, José-Ignacio Riezu-Boj, and J. Alfredo Martínez
Springer Science and Business Media LLC
AbstractInsulin resistance (IR) is a hallmark of type 2 diabetes, metabolic syndrome and cardiometabolic risk. An epigenetic phenomena such as DNA methylation might be involved in the onset and development of systemic IR. The aim of this study was to explore the genetic DNA methylation levels in peripheral white blood cells with the objective of identifying epigenetic signatures associated with IR measured by the Homeostatic Model Assessment of IR (HOMA-IR) following an epigenome-wide association study approach. DNA methylation levels were assessed using Infinium Methylation Assay (Illumina), and were associated with HOMA-IR values of participants from the Methyl Epigenome Network Association (MENA) project, finding statistical associations for at least 798 CpGs. A stringent statistical analysis revealed that 478 of them showed a differential methylation pattern between individuals with HOMA-IR ≤ 3 and > 3. ROC curves of top four CpGs out of 478 allowed differentiating individuals between both groups (AUC≈0.88). This study demonstrated the association between DNA methylation in some specific CpGs and HOMA-IR values that will help to the understanding and in the development of new strategies for personalized approaches to predict and prevent IR-associated diseases.
Mirian Samblas, Maria Luisa Mansego, Maria Angeles Zulet, Fermín I. Milagro, and J. Alfredo Martinez
Springer Science and Business Media LLC
Ana Arpón, Fermín I. Milagro, Omar Ramos-Lopez, Maria L. Mansego, José-Ignacio Riezu-Boj, and J. Alfredo Martínez
MDPI AG
Epigenetic signatures such as DNA methylation may be associated with specific obesity traits in different tissues. The onset and development of some obesity-related complications are often linked to visceral fat accumulation. The aim of this study was to explore DNA methylation levels in peripheral white blood cells to identify epigenetic methylation marks associated with waist circumference (WC). DNA methylation levels were assessed using Infinium Human Methylation 450K and MethylationEPIC beadchip (Illumina) to search for putative associations with WC values of 473 participants from the Methyl Epigenome Network Association (MENA) project. Statistical analysis and Ingenuity Pathway Analysis (IPA) were employed for assessing the relationship between methylation and WC. A total of 669 CpGs were statistically associated with WC (FDR < 0.05, slope ≥ |0.1|). From these CpGs, 375 CpGs evidenced a differential methylation pattern between females with WC ≤ 88 and > 88 cm, and 95 CpGs between males with WC ≤ 102 and > 102 cm. These differentially methylated CpGs are located in genes related to inflammation and obesity according to IPA. Receiver operating characteristic (ROC) curves of the top four significant differentially methylated CpGs separated by sex discriminated individuals with presence or absence of abdominal fat. ROC curves of all the CpGs from females and one CpG from males were validated in an independent sample (n = 161). These methylation results add further insights about the relationships between obesity, adiposity-associated comorbidities, and DNA methylation where inflammation processes may be involved.
Francisca Salas-Pérez, Omar Ramos-Lopez, María L. Mansego, Fermín I. Milagro, José L. Santos, José I. Riezu-Boj, and J. Alfredo Martínez
Impact Journals, LLC
Aging is the main risk factor for most chronic diseases. Epigenetic mechanisms, such as DNA methylation (DNAm) plays a pivotal role in the regulation of physiological responses that can vary along lifespan. The aim of this research was to analyze the association between leukocyte DNAm in genes involved in longevity and the occurrence of obesity and related metabolic alterations in an adult population. Subjects from the MENA cohort (n=474) were categorized according to age (<45 vs 45>) and the presence of metabolic alterations: increased waist circumference, hypercholesterolemia, insulin resistance, and metabolic syndrome. The methylation levels of 58 CpG sites located at genes involved in longevity-regulating pathways were strongly correlated (FDR-adjusted< 0.0001) with BMI. Fifteen of them were differentially methylated (p<0.05) between younger and older subjects that exhibited at least one metabolic alteration. Six of these CpG sites, located at MTOR (cg08862778), ULK1 (cg07199894), ADCY6 (cg11658986), IGF1R (cg01284192), CREB5 (cg11301281), and RELA (cg08128650), were common to the metabolic traits, and CREB5, RELA, and ULK1 were statistically associated with age. In summary, leukocyte DNAm levels of several CpG sites located at genes involved in longevity-regulating pathways were associated with obesity and metabolic syndrome traits, suggesting a role of DNAm in aging-related metabolic alterations.
Maria L. Mansego, Fermín I. Milagro, and J. Alfredo Martínez
Elsevier
M. Samblas, F. I. Milagro, M. L. Mansego, A. Marti, J. A. Martinez, and
Wiley
SummaryBackgroundThe global prevalence of childhood overweight and obesity has increased in the last years. Epigenetic dysregulation affecting gene expression could be a determinant in early‐life obesity onset and accompanying complications.ObjectiveThe aim of the present investigation was to analyse the putative association between DNA methylation and childhood obesity.MethodsDNA was isolated from white blood cells of 24 children obtained from the GENOI study and was hybridized in a 450K methylation array. Two CpG sites associated with obesity were validated in 91 children by MassArray® EpiTyper™ technology.ResultsGenome‐wide analysis identified 734 CpGs (783 genes) differentially methylated between cases (n = 12) and controls (n = 12). Ingenuity Pathway Analysis showed that these genes were involved in oxidative stress and circadian rhythm signalling pathways. Moreover, the DNA methylation levels of VIPR2, GRIN2D, ADCYAP1R1, PER3 and PTPRS regions correlated with the obesity trait. EpiTyper™ validation also identified significant correlations between methylation levels of CpG sites on PTPRS and PER3 with BMI z‐score.ConclusionsThis study identified several CpG sites and specifically several CpGs in the PTPRS and PER3 genes differentially methylated between obese and non‐obese children, suggesting a role for DNA methylation concerning development of childhood obesity.
Omar Ramos-Lopez, Mirian Samblas, Fermin I. Milagro, M. Angeles Zulet, Maria L. Mansego, Jose I. Riezu-Boj, and J. Alfredo Martinez
Elsevier BV
O. Ramos-Lopez, A. Arpón, J.I. Riezu-Boj, F.I. Milagro, M.L. Mansego, J.A. Martinez, I. Abete, A.B. Crujeiras, M. Cuervo, L. Goni,et al.
Elsevier BV
Amaya Lopez-Pascual, Arrate Lasa, María P. Portillo, Fernando Arós, María L. Mansego, Pedro González-Muniesa, and J. Alfredo Martinez
S. Karger AG
<b><i>Background:</i></b> Deoxyribonucleic acid (DNA) methylation is an epigenetic modification involved in gene expression regulation, usually via gene silencing, which contributes to the risks of many multifactorial diseases. The aim of the present study was to analyze the influence of resting oxygen consumption on global and gene DNA methylation as well as protein secretion of inflammatory markers in blood cells from obese subjects with sleep apnea-hypopnea syndrome (SAHS). <b><i>Methods:</i></b> A total of 44 obese participants with SAHS were categorized in 2 groups according to their resting oxygen consumption. DNA methylation levels were evaluated using a methylation-sensitive high resolution melting approach. <b><i>Results:</i></b> The analyzed interleukin 6 (<i>IL6</i>) gene cytosine phosphate guanine (CpG) islands showed a hypomethylation, while serum IL-6 was higher in the low compared to the high oxygen consumption group (<i>p</i> < 0.05). Moreover, an age-related loss of DNA methylation of tumor necrosis factor (B = -0.82, 95% CI -1.33 to -0.30) and long interspersed nucleotide element 1 (B = -0.46; 95% CI -0.87 to -0.04) gene CpGs were found. Finally, studied CpG methylation levels of serpin peptidase inhibitor, clade E member 1 (<i>r</i> = 0.43;<i> p</i> = 0.01), and <i>IL6</i> (<i>r = </i>0.41; <i>p</i> = 0.02) were positively associated with fat-free mass. <b><i>Conclusions:</i></b> These findings suggest a potential role of oxygen in the regulation of inflammatory genes. Oxygen consumption measurement at rest could be proposed as a clinical biomarker of metabolic health.
M.L. Mansego, M. Garcia‐Lacarte, F.I. Milagro, A. Marti, J.A. Martinez, and
Wiley
SummaryBackgroundEpigenetic mechanisms may be involved in obesity onset and its consequences. The aim of the present study was to evaluate whether DNA methylation status in microRNA (miRNA) coding regions is associated with childhood obesity.Material and MethodsDNA isolated from white blood cells of 24 children (identification sample: 12 obese and 12 non‐obese) from the Grupo Navarro de Obesidad Infantil study was hybridized in a 450 K methylation microarray. Several CpGs whose DNA methylation levels were statistically different between obese and non‐obese were validated by MassArray® in 95 children (validation sample) from the same study.ResultsMicroarray analysis identified 16 differentially methylated CpGs between both groups (6 hypermethylated and 10 hypomethylated). DNA methylation levels in miR‐1203, miR‐412 and miR‐216A coding regions significantly correlated with body mass index standard deviation score (BMI‐SDS) and explained up to 40% of the variation of BMI‐SDS. The network analysis identified 19 well‐defined obesity‐relevant biological pathways from the KEGG database. MassArray® validation identified three regions located in or near miR‐1203, miR‐412 and miR‐216A coding regions differentially methylated between obese and non‐obese children.ConclusionsThe current work identified three CpG sites located in coding regions of three miRNAs (miR‐1203, miR‐412 and miR‐216A) that were differentially methylated between obese and non‐obese children, suggesting a role of miRNA epigenetic regulation in childhood obesity.
Júlia Cristina Cardoso Carraro, Helen Hermana Miranda Hermsdorff, Maria Luisa Mansego, Maria Ángeles Zulet, Fermín I. Milagro, Josefina Bressan, and J. Alfredo Martínez
S. Karger AG
<b><i>Background/Aim:</i></b> This study hypothesized an association between healthy dietary patterns, hypermethylation of the tumor necrosis factor-α <i>(TNF-α)</i> promoter and decreased risk of metabolic changes. <b><i>Methods:</i></b> Forty normal-weight young women were involved in this cross-sectional study. DNA was isolated from white blood cells, and CpG site methylation in <i>TNF-α</i> was analyzed by Sequenom EpiTyper. The quality of the diet was assessed by Healthy Eating Index (HEI-2005). <b><i>Results:</i></b> Contradicting our hypothesis, HEI-2005 score was negatively associated with CpG5 (r = -0.460, p = 0.003) and<i> TNF-α</i> total methylation (r = -0.355, p = 0.026). A higher intake of fruits was related to lower insulin, HOMA-IR, and <i>TNF-α</i> methylation. No other dietary pattern was related to <i>TNF-α</i> methylation. <i>TNF-α</i> total methylation correlated positively with systolic blood pressure (r = 0.323; p = 0.042) and CpG5 methylation with body mass index (r = 0.333, p = 0.036). Furthermore, fiber intake was negatively associated with the CpG5 (r = -0.324, p = 0.041) and <i>TNF-α</i> total methylation (r = -0.434, p = 0.005), whereas vitamin C intake was negatively associated with <i>TNF-α </i>total methylation (r = -0.411, p = 0.009). Intakes of apples and citrus fruits were negatively associated with <i>TNF-α</i> total methylation. <b><i>Conclusion:</i></b> A healthy dietary pattern and higher fruit intake (particularly apples and citrus fruits) were related to better glucose tolerance in healthy subjects, which could be mediated by lower <i>TNF-α</i> methylation.
Júlia Cristina Cardoso Carraro, Maria Luisa Mansego, Fermin Ignacio Milagro, Larissa Oliveira Chaves, Fernanda Carvalho Vidigal, Josefina Bressan, and J. Alfredo Martínez
Informa UK Limited
Abstract We analyzed whether global and inflammatory genes methylation can be early predictors of metabolic changes and their associations with the diet, in a cross-sectional study (n = 40). Higher global methylation was associated to adiposity, insulin resistance, and lower quality of the diet. Methylation of IL-6, SERPINE1 and CRP genes was related to adiposity traits and macronutrients intake. SERPINE1 hypermethylation was also related to some metabolic alterations. CRP methylation was a better predictor of insulin resistance than CRP plasma concentrations. Global and inflammatory gene promoter hypermethylation can be good early biomarkers of adiposity and metabolic changes and are associated to the quality of the diet.
Vannina G. Marrachelli, Pilar Rentero, María L. Mansego, Jose Manuel Morales, Inma Galan, Mercedes Pardo-Tendero, Fernando Martinez, Juan Carlos Martin-Escudero, Laisa Briongos, Felipe Javier Chaves,et al.
Public Library of Science (PLoS)
Background To identify metabolomic and genomic markers associated with the presence of clustering of cardiometabolic risk factors (CMRFs) from a general population. Methods and Findings One thousand five hundred and two subjects, Caucasian, > 18 years, representative of the general population, were included. Blood pressure measurement, anthropometric parameters and metabolic markers were measured. Subjects were grouped according the number of CMRFs (Group 1: <2; Group 2: 2; Group 3: 3 or more CMRFs). Using SNPlex, 1251 SNPs potentially associated to clustering of three or more CMRFs were analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age 54±19, 50.6% men) with high genotyping call rate were analysed. A differential metabolomic profile, which included products from mitochondrial metabolism, extra mitochondrial metabolism, branched amino acids and fatty acid signals were observed among the three groups. The comparison of metabolomic patterns between subjects of Groups 1 to 3 for each of the genotypes associated to those subjects with three or more CMRFs revealed two SNPs, the rs174577_AA of FADS2 gene and the rs3803_TT of GATA2 transcription factor gene, with minimal or no statistically significant differences. Subjects with and without three or more CMRFs who shared the same genotype and metabolomic profile differed in the pattern of CMRFS cluster. Subjects of Group 3 and the AA genotype of the rs174577 had a lower prevalence of hypertension compared to the CC and CT genotype. In contrast, subjects of Group 3 and the TT genotype of the rs3803 polymorphism had a lower prevalence of T2DM, although they were predominantly males and had higher values of plasma creatinine. Conclusions The results of the present study add information to the metabolomics profile and to the potential impact of genetic factors on the variants of clustering of cardiometabolic risk factors.
Marcos Garcia-Lacarte, Fermin I. Milagro, Maria A. Zulet, J. Alfredo Martinez, and Maria L. Mansego
Informa UK Limited
Objectives: Epigenetic markers, and in particular DNA methylation, have come to the fore as new tools in the personalization of the treatment of obesity and its comorbidities. The objectives of the current investigation were to identify epigenetic biomarkers that might be predictive of response to a weight-loss intervention, and to better understand the influence of certain nutrients (particularly antioxidants) on the epigenome. Methods: Global DNA (LINE-1) methylation levels were assessed in peripheral blood mononuclear cells (PBMCs) from 96 obese volunteers of the Metabolic Syndrome Reduction in Navarra study, using a methylation-sensitive high resolution melting approach after bisulfite modification. Results: Baseline LINE-1 DNA methylation levels were significantly higher (5.41%) in high responders (>8% of weight loss) as compared to low responders (<8%) to the energy-restricted treatment. Indeed, a LINE-1 methylation higher than 84.15% may be predictive of a high response to the hypocaloric diet. Statistically significant correlations were found between LINE-1 baseline DNA methylation levels and the response to the treatment involving total fat mass and body weight. Furthermore, LINE-1 baseline methylation levels positively correlated with baseline dietary total antioxidant capacity (TAC). Discussion: LINE-1 methylation levels in PBMCs might be used to predict response to a dietary weight-loss intervention, and seem to be related to the dietary TAC. Trial Registration: www.clinicaltrials.gov: NCT01087086.
Carolina Ferreira Nicoletti, Carla Barbosa Nonino, Bruno Affonso Parenti de Oliveira, Marcela Augusta de Souza Pinhel, Maria Luisa Mansego, Fermin Ignacio Milagro, Maria Angeles Zulet, and José Alfredo Martinez
Springer Science and Business Media LLC
José Luiz Marques-Rocha, Fermin I. Milagro, Maria Luisa Mansego, Denise Machado Mourão, J. Alfredo Martínez, and Josefina Bressan
Informa UK Limited
Abstract With the goal of investigating if epigenetic biomarkers from white blood cells (WBC) are associated with dietary, anthropometric, metabolic, inflammatory and oxidative stress parameters in young and apparently healthy individuals. We evaluated 156 individuals (91 women, 65 men; age: 23.1±3.5 years; body mass index: 22.0±2.9 kg/m2) for anthropometric, biochemical and clinical markers, including some components of the antioxidant defense system and inflammatory response. DNA methylation of LINE-1, TNF-α and IL-6 and the expression of some genes related to the inflammatory process were analyzed in WBC. Adiposity was lower among individuals with higher LINE-1 methylation. On the contrary, body fat-free mass was higher among those with higher LINE-1 methylation. Individuals with higher LINE-1 methylation had higher daily intakes of calories, iron and riboflavin. However, those individuals who presented lower percentages of LINE-1 methylation reported higher intakes of copper, niacin and thiamin. Interestingly, the group with higher LINE-1 methylation had a lower percentage of current smokers and more individuals practicing sports. On the other hand, TNF-α methylation percentage was negatively associated with waist girth, waist-to-hip ratio and waist-to-stature ratio. Plasma TNF-α levels were lower in those individuals with higher TNF-α methylation. This study suggests that higher levels of LINE-1 and TNF-α methylation are associated with better indicators of adiposity status in healthy young individuals. In addition, energy and micronutrient intake, as well as a healthy lifestyle, may have a role in the regulation of DNA methylation in WBC and the subsequent metabolic changes may affect epigenetic biomarkers.
José Luiz Marques-Rocha, Fermin I. Milagro, Maria Luisa Mansego, Maria Angeles Zulet, Josefina Bressan, and J. Alfredo Martínez
Elsevier BV
Maria L. Mansego, Griselda De Marco, Carmen Ivorra, Raúl Lopez-Izquierdo, Sonsoles Morcillo, Gemma Rojo-Martínez, Verónica González-Albert, Fernando Martinez, Federico Soriguer, Juan C. Martín-Escudero,et al.
Springer Science and Business Media LLC
Itziar Abete, Ana M. Gomez-Uriz, Maria Mansego, Ana Arce, Estibaliz Goyenechea, Vanessa Blazquez, Maria Martinez-Zabaleta, Pedro Gonzalez-Muniesa, Adolfo De Munain, J. Alfredo Martinez,et al.
Bentham Science Publishers Ltd.
Ischemic stroke patients often show high concentrations of circulating inflammatory markers that are associated with increased risk of recurrence. Epigenetic mechanisms could be involved in obesity, inflammation and stroke. The objective of this research was to investigate, in obese patients suffering a previous stroke, the effects of a nutritional program on anthropometric and biochemical variables, and on the methylation patterns of two stroke-related genes (KCNQ1: potassium channel, voltage gated KQT-like subfamily Q, member 1; and WT1: Wilms tumor 1). Twenty-two ischemic stroke patients were compared with a control group composed of eighteen obese subjects with similar age and body mass index ranges. Both groups followed a 20-week nutritional program based on an energy-restricted balanced diet with high adherence to the Mediterranean dietary pattern. The intervention significantly improved anthropometric and metabolic variables, such as the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein concentration, in ischemic stroke patients, and was accompanied by changes in the methylation patterns of both stroke-related genes, which correlated with anthropometric and biochemical variables.
María Mansego, Fermín Milagro, María Zulet, María Moreno-Aliaga, and José Martínez
MDPI AG
The aim of this study was to evaluate whether genome-wide levels of DNA methylation are associated with age and the health risks of obesity (HRO); defined according to BMI categories as “Low HRO” (overweight and class 1 obesity) versus “High HRO” (class 2 and class 3 obesity). Anthropometric measurements were assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in Navarra (RESMENA) study and 24 women from another independent study, Effects of Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP study). In the pooled population; the methylation levels of 55 CpG sites were significantly associated with age after Benjamini-Hochberg correction. In addition, DNA methylation of three CpG sites located in ELOVL2; HOXC4 and PI4KB were further negatively associated with their mRNA levels. Although no differentially methylated CpG sites were identified in relation to HRO after multiple testing correction; several nominally significant CpG sites were identified in genes related to insulin signaling; energy and lipid metabolism. Moreover, statistically significant associations between BMI or mRNA levels and two HRO-related CpG sites located in GPR133 and ITGB5 are reported. As a conclusion, these findings from two Spanish cohorts add knowledge about the important role of DNA methylation in the age-related regulation of gene expression. In addition; a relevant influence of age on DNA methylation in white blood cells was found, as well as, on a trend level, novel associations between DNA methylation and obesity.
Ana M. Gómez-Úriz, Fermín I. Milagro, María L. Mansego, Paúl Cordero, Itziar Abete, Ana De Arce, Estíbaliz Goyenechea, Vanessa Blázquez, Maite Martínez-Zabaleta, José Alfredo Martínez,et al.
Oxford University Press (OUP)
Obesity and stroke are multifactorial diseases in which genetic, epigenetic and lifestyle factors are involved. The research aims were, first, the description of genes with differential epigenetic regulation obtained by an 'omics' approach in patients with ischemic stroke and, second, to determine the importance of some regions of these selected genes in biological processes depending on the body mass index. A case-control study using two populations was designed. The first population consisted of 24 volunteers according to stroke/non-stroke and normal weight/obesity conditions. The second population included 60 stroke patients and 55 controls classified by adiposity. DNA from the first population was analyzed with a methylation microarray, showing 80 cytosine-guanine dinucleotides (CpG) sites differentially methylated in stroke and 96 CpGs in obesity, whereas 59 CpGs showed interaction. After validating these data by MassArray Epityper, the promoter region of peptidase M20 domain containing 1 (PM20D1) gene was significantly hypermethylated in stroke patients. One CpG site at Caldesmon 1 (CALD1) gene showed an interaction between stroke and obesity. Two CpGs located in the genes Wilms' tumor 1 (WT1) and potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) were significantly hypermethylated in obese patients. In the second population, KCNQ1 was also hypermethylated in the obese subjects. Two CpGs of this gene were subsequently validated by methylation-sensitive high-resolution melting. Moreover, KCNQ1 methylation levels were associated with plasma KCNQ1 protein concentrations. In conclusion, obesity induced changes in the KCNQ1 methylation pattern which were also dependent on stroke. Furthermore, the epigenetic marks differentially methylated in the stroke patients were dependent on the previous obese state. These DNA methylation patterns could be used as future potential stroke biomarkers.
Aurora Perez-Cornago, Maria Mansego, María Zulet, and José Martinez
MDPI AG
Understanding the regulation of gene activities depending on DNA methylation has been the subject of much recent study. However, although polymorphisms of the HTR2A gene have been associated with both obesity and psychiatric disorders, the role of HTR2A gene methylation in these illnesses remains uncertain. The aim of this study was to evaluate the association of HTR2A gene promoter methylation levels in white blood cells (WBC) with obesity traits and depressive symptoms in individuals with metabolic syndrome (MetS) enrolled in a behavioural weight loss programme. Analyses were based on 41 volunteers (mean age 49 ± 1 year) recruited within the RESMENA study. Depressive symptoms (as determined using the Beck Depression Inventory), anthropometric and biochemical measurements were analysed at the beginning and after six months of weight loss treatment. At baseline, DNA from WBC was isolated and cytosine methylation in the HTR2A gene promoter was quantified by a microarray approach. In the whole-study sample, a positive association of HTR2A gene methylation with waist circumference and insulin levels was detected at baseline. Obesity measures significantly improved after six months of dietary treatment, where a lower mean HTR2A gene methylation at baseline was associated with major reductions in body weight, BMI and fat mass after the treatment. Moreover, mean HTR2A gene methylation at baseline significantly predicted the decrease in depressive symptoms after the weight loss treatment. In conclusion, this study provides newer evidence that hypermethylation of the HTR2A gene in WBC at baseline is significantly associated with a worse response to a weight-loss intervention and with a lower decrease in depressive symptoms after the dietary treatment in subjects with MetS.
Vannina G. Marrachelli, Daniel Monleon, Pilar Rentero, María L. Mansego, Jose Manuel Morales, Inma Galan, Remedios Segura, Fernando Martinez, Juan Carlos Martin-Escudero, Laisa Briongos,et al.
Public Library of Science (PLoS)
To identify factors related with the risk to develop microalbuminuria using combined genomic and metabolomic values from a general population study. One thousand five hundred and two subjects, Caucasian, more than 18 years, representative of the general population, were included. Blood pressure measurement and albumin/creatinine ratio were measured in a urine sample. Using SNPlex, 1251 SNPs potentially associated to urinary albumin excretion (UAE) were analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age 54±19, 50.6% men, ACR>30 mg/g in 81 subjects) with high genotyping call rate were analysed. A characteristic metabolomic profile, which included products from mitochondrial and extra mitochondrial metabolism as well as branched amino acids and their derivative signals, were observed in microalbuminuric as compare to normoalbuminuric subjects. The comparison of the metabolomic profile between subjects with different UAE status for each of the genotypes associated to microalbuminuria revealed two SNPs, the rs10492025_TT of RPH3A gene and the rs4359_CC of ACE gene, with minimal or no statistically significant differences. Subjects with and without microalbuminuria, who shared the same genotype and metabolomic profile, differed in age. Microalbuminurics with the CC genotype of the rs4359 polymorphism and with the TT genotype of the rs10492025 polymorphism were seven years older and seventeen years younger, respectively as compared to the whole microalbuminuric subjects. With the same metabolomic environment, characteristic of subjects with microalbuminuria, the TT genotype of the rs10492025 polymorphism seems to increase and the CC genotype of the rs4359 polymorphism seems to reduce risk to develop microalbuminuria.