Rs9939609 Polymorphism Research Articles

PNPLA3 and SAMM50 variants are associated with lean nonalcoholic fatty liver disease in Asian population

Lean adults with nonalcoholic fatty liver disease (NAFLD) have a higher risk of metabolic syndrome than lean controls. The study aimed to investigate the clinical and genetic features of lean NAFLD which remain unclear in Asian populations. This was a genetic cohort study conducted in the HAVO Health Exam Clinic in 2020-2021 in Taiwan. Adults with a body mass index less than 24 kg/m2 were enrolled. Fatty liver was defined by ultrasonography. The candidate gene approach was based on the library of the NHGRI-EBI website. After removing duplication and nonsignificant variants, rs738409 in the PNPLA3 gene and rs3761472 in the SAMM50 gene were chosen. Multiple logistic regression models and receiver operating characteristic (ROC) curves were used. A total of 1652 lean controls and 602 lean NAFLD patients were enrolled. The average age was 43.8±11.5 years. Lean NAFLD subjects were older and had a higher percentage of metabolic syndrome (case vs. control: 10.5% vs. 1.5%). The GG genotypes of PNPLA3 rs12483959 (OR: 3.06; 95% CI: 2.15-4.37) and SAMM50 rs3761472 (OR: 2.90; 95% CI: 2.04-4.14) had a higher risk of fatty liver after adjusting for BMI and metabolic syndrome. The areas under the ROC curve for PNPLA3 rs738409 and SAMM50 rs3761472 in the detection of lean NAFLD were 0.859 (95%CI: 0.841, 0.877) and 0.860 (95%CI: 0.843, 0.877), respectively. PNPLA3 rs738409 and SAMM50 rs3761472 gene polymorphisms are associated with a higher risk of fatty liver in lean individuals independent of BMI and metabolic syndrome in Asian populations.

Analysis of metabolites associated with ADIPOQ genotypes in individuals with type 2 diabetes mellitus

Diabetes mellitus (DM) is a significant public health problem and it is known that the identification of molecular markers involved in glycemic control can impact disease control. Although the rs266729 polymorphism located in the promoter of the adiponectin gene (ADP) has been shown to be a candidate for involvement in glycemic control, the genotypic groups have never been characterized in terms of metabolomic aspects. Objective: Analyze the metabolites present in the rs266729 genotype groups. 127 diabetic individuals were compared according to the rs266729 genotype groups CC and GC + GG (RFLP-PCR). Blood plasma metabolites were classified by nuclear magnetic resonance (NMR), and the metabolic pathways of each group using the MetaboAnalyst tool. Insulin therapy (p = 0.049) was more frequent in the GC + GG rs266729 group. Lactate, alanine, glutamine, aspartate, lipid, lysine, isoleucine, citrulline, cholesterol, and fucose impacted the CC group and aspartate, beta-glucose, glutamate, pyruvate, proline, and 2-oxoglutarate impacted the CG + GG group. The glucose-alanine pathway, malate-aspartate transport, and urea cycle impacted the CC group (D-glucose, glutamic acid, L-alanine, oxoglutaric acid, and pyruvic acid). The glutamine/glutamate ratio is likely to be related to the causes of rs266729 influencing the risk of diabetes.

Correlation of Eight (8) Polymorphisms and Their Genotypes with the Risk Factors of Cardiovascular Disease in a Black Elderly Population.

Single nucleotide polymorphisms (SNPs) have been associated with the development of cardiovascular diseases (CVDs). This study correlated eight SNPs with the risk factors of CVD in a black elderly population. Genotyping was used to detect eight polymorphisms; rs675 (ApoA-IV), rs699 (Angiotensinogen (AGT)), rs247616 and rs1968905 (Cholesteryl ester transfer protein (CETP)), rs1801278 (Insulin receptor substrate 1 (IRS-1)), rs1805087 (Methylenetetrahydrofolate reductase (MTHFR)) and rs28362286 and rs67608943 (Proprotein convertase subtilisin/kexin type 9 (PCSK9)), as well as their genotypes in deoxyribonucleic acid (DNA) extracted from peripheral blood. The cardiovascular risk (CVR) measurements were conducted on a Konelab 20i Thermo Scientific autoanalyzer and an enzyme-linked immunoassay (ELISA) assay. International Business Machines Corporation (IBM)® Statistical Package for the Social Sciences ® (SPSS) version 28 was used for statistical analysis. The heterozygous and homozygous genotypes of the eight polymorphisms were detected with the corresponding CVD risk factors. Subgroup analysis indicated that certain genotype carriers exhibited variations in their concentrations of CVR factors compared to others; however, these differences did not reach statistical significance. For example, carriers of the G genotype of the rs699 polymorphism showed marginally different blood pressure readings compared to the AG genotype carriers. The multiple linear regression analysis indicated that the only significant association was between PCSK9 and the rs28362286 (p = 0.029) polymorphism. The findings of our study show that single nucleotide polymorphisms are disseminated across the human genome. The heterozygous and homozygous genotypes of the SNPs require further investigation as they may have independent and possible collective roles in increasing the risk of CVDs.

Association of rs35767 polymorphism in the IGF1 gene with athletic performance in power and endurance sports: A meta-analysis

BackgroundSport performance is a multifactorial phenotype dependent on the interaction of multiple genetic and non-genetic factors. More than 200 polymorphisms have been associated with athletic performance. The single nucleotide polymorphism (SNP) rs35767, located in the regulatory region of the IGF1 gene, influences its expression and has been associated with sports-related phenotypes. We aimed to perform a meta-analysis to evaluate the association between the rs35767 polymorphism of the IGF1 gene and athletic performance in power and endurance sports. MethodsLiterature has been retrieved from PubMed, Web of Science, Scopus, Embase, and Sport Discus databases until October 2023. This study was designed according to the PRISMA statement. Different models were tested, and heterogeneity was evaluated. ResultsThree studies were included in this meta-analysis. Statistically significant differences were highlighted for the frequency of the minor allele when comparing all athletes and controls (p < 0.001; OR = 1.74; 95 % CI = 1.26–2.40), endurance athletes and controls (p = 0.016; OR = 1.87; 95 % CI = 1.12–3.1) and power sport athletes and controls (p = 0.007; OR = 1.62; 95 % CI = 1.14–2.31). No statistically significant difference was found between the power and endurance groups. According to data analysis, the recessive model is the most suitable genetic model. ConclusionsThis metanalysis supports the role of the minor allele of the rs35767 polymorphism of the IGF1 gene as favoring an athlete's performance in endurance and power sports.

Effect of FTO Gene polymorphism on anthropometric, hemodynamic, and autonomic variables in adolescents

Objective: The study aimed to analyze the influence of physical activity levels and the rs9939609 polymorphism (FTO gene) on anthropometric, hemodynamic, and cardiac autonomic variables in public school students. Methods: A total of 288 students (aged 11 to 18, both sexes) from public schools in São Luís, Maranhão, were divided into four groups: sedentary AA+AT (AA+AT sed), active AA+AT (AA+AT activ), sedentary TT (TT sed), and active TT (TT activ). Evaluations included the International Physical Activity Questionnaire, weight, height, body mass index (BMI), buccal cells collection for DNA extraction, systolic (SBP) and diastolic (DBP) blood pressure measurements, and heart rate variability (HRV) analysis. A chi-square test for allelic associations was applied a 5% significance level. Results: No significant differences were observed in DBP or heart rate (HR). The active groups (AA+AT activ and TT activ) exhibited reductions in weight and METs/min/week compared to their respective sedentary groups (P&lt;0.05). The TT activ group also demonstrated reductions in SBP and BMI compared to the TT sed group (P&lt;0.05). The TT activ group had higher HRV in the RR time domain (ms) compared to the TT sed group (P&lt;0.05), though no significant differences were found in other HRV variables. Conclusions: The FTO gene polymorphism influences cardiac autonomic modulation, while physical activity levels affect anthropometric variables.

Association of FTO variants rs9939609 and rs1421085 with elevated sugar and fat consumption in adult obesity

This cross-sectional study explores the impact of FTO gene single nucleotide polymorphisms (SNPs) rs9939609 and rs1421085 on dietary habits contributing to obesity risk in Thai adults. The study enrolled 384 participants from Bangkok, categorized as non-obese (BMI < 25 kg/m2) or obese (BMI ≥ 25 kg/m2) based on WHO Asia Pacific Guidelines. Genotyping for FTO variants was performed using DNA from blood samples. While both SNPs adhered to Hardy–Weinberg equilibrium, the association between risk alleles and anthropometric measurements was not statistically significant. However, risk allele carriers showed significantly higher intakes of sugar and saturated fat compared to homozygous dominant individuals. In the obese group, the odds ratio for high-sugar intake was 2.22 (95% CI 1.13–4.37, p = 0.021) for rs9939609 risk allele carriers. For high-saturated fat intake, the odds ratio was 1.86 (95% CI 1.02–3.40, p = 0.041). Similar associations were observed for rs1421085. Risk allele carriers also exhibited significantly higher leptin levels (p < 0.043) and a positive correlation with myeloperoxidase levels (p < 0.038). These findings highlight the complex relationship between FTO risk alleles, increased consumption of sugar and saturated fat, and obesity-related parameters. The insights emphasize the importance of considering both genetic and dietary factors in obesity prevention strategies.

Significance of the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism on non alcoholic fatty liver disease

Significance of the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism on non alcoholic fatty liver disease

Genetic Predisposition to Prediabetes in the Kazakh Population.

The aim of this study was to conduct a comparative analysis of the population frequencies of the minor allele of polymorphic variants in the genes TCF7L2 (rs7903146) and PPARG (rs1801282), based on the genome-wide association studies analysis data associated with the risk of developing prediabetes, in an ethnically homogeneous Kazakh population compared to previously studied populations worldwide. This study utilized a genomic database consisting of 1800 ethnically Kazakh individuals who were considered in healthy condition. Whole-genome genotyping was performed using Illumina OmniChip 2.5-8 arrays, which interrogated approximately 2.5 million single nucleotide polymorphisms. The distribution of genotypes for the TCF7L2 (rs7903146) and PPARG (rs1801282) polymorphisms in the Kazakh sample was found to be in Hardy-Weinberg equilibrium (p > 0.05). The minor G allele of the "Asian" protective polymorphism rs1801282 in the PPARG gene was observed at a frequency of 13.8% in the Kazakh population. This suggests a potentially more significant protective effect of this polymorphism in reducing the risk of prediabetes among Kazakhs. The frequency of the unfavorable T allele of the insulin secretion-disrupting gene TCF7L2 (rs7903146) in Kazakhs was 15.2%. Studying the associations of genetic markers for prediabetes enables the timely identification of "high-risk groups" and facilitates the implementation of effective preventive measures. Further results from replicative genomic research will help identify significant polymorphic variants of genes underlying the alteration of prediabetes status.

Study of adiponectin gene (rs1501299) polymorphism and serum adiponectin level in patients with primary knee osteoarthritis

BackgroundWe aimed to study, for the first time in the Egyptian population, the relationship between the serum adiponectin level in knee osteoarthritis (KOA) patients and its correlation with clinical, radiological, and ultrasonographic characteristics. Additionally, investigate the relationship between the adiponectin (ADIPOQ) gene rs1501299 (+ 276G/T) polymorphism and KOA susceptibility and severity.MethodsThis case-control study enrolled 40 patients with primary KOA and 40 matched controls. All patients underwent physical examination of the knee, pain assessment using the visual analogue scale (VAS), and functional evaluation by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Severity of KOA was assessed by Kellgren Lawrence (KL) grading scale and ultrasonography grading systems. Serum adiponectin levels and adiponectin (ADIPOQ) gene single nucleotide polymorphism (SNP) (rs1501299) genotyping were done for all patients and controls.ResultsThe study included 40 patients with primary symptomatic KOA and 40 controls with comparable age, sex, and body mass index. The genotype of the rs1501299 (+ 276G/T) polymorphism of the ADIPOQ gene was determined using TaqMan allelic discrimination. An enzyme-linked immunosorbent test was used to measure the level of serum adiponectin. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score was used to assess functional capability, while the visual analogue scale was utilised to assess knee pain. Using the Kellgren-Lawrence (KL) grading method and global femoral cartilage (GFC) ultrasound grading, the severity of KOA was assessed. No significant differences between patients and controls as regards the genotype distributions and allele frequencies (p = 0.400, p = 0.507, respectively) of ADIPOQ gene rs1501299 (+ 276G/T) polymorphism. Furthermore, serum adiponectin level was significantly higher in the patients compared to healthy subjects (p < 0.001). Additionally, adiponectin level had a significant negative correlation with disease severity as evaluated by KL and GFC grading (r=-0.351, p = 0.027 and r=-0.397, p = 0.011, respectively).ConclusionsThe ADIPOQ gene rs1501299 (+ 276G/T) polymorphism was not associated with KOA severity or vulnerability. The level of adiponectin considerably reduced as the severity of KOA rose, indicating that adiponectin may have a preventive effect in KOA.

Investigation of the relationship between adiponectin gene polymorphism (ADIPOQ SNP rs-266729) and obesity Patients / Basra-Iraqi

Adiponectin is one of the most important hormones secreted by adipose tissue and plays a major role in the development of obesity. A variant-specific ADIPOQ single nucleotide polymorphism (SNP rs-266729) with a C to G missense mutation can be strongly associated with obesity. Therefore, this study aims to evaluate the association of single nucleotide polymorphisms (SNP rs-266729) of the ADIPOQ gene with obesity and some biochemical markers in these patients. The case-control study included 186 participants (106 patients and 80 healthy control). DNA was extracted from whole blood and then the Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP-PCR) technique was used to limit the genotype of the ADIPOQ gene (rs266729) polymorphism. Also, the lipid profile, glycated hemoglobin (HbA1C), fasting blood glucose (FBG), insulin, and adiponectin were measured by standard methods. Results: The allele G in the ADIPOQ-gene polymorphism (rs266729) was a significantly higher frequency of 23 (21.6%) in the obese patients (P_Value = 0.039) compared with the control subject of 10 (12.5%). It significantly increased the risk in the additive model and allele frequency (P = 0.0139 and 0.0133), respectively. The rs266729 SNP showed a significant association with increased BMI, insulin, HOMO-IR, TG, VLDL, and lower adiponectin at a p-value of 0.001 for all, after adjustments for age and sex. Lower levels of high-density lipoprotein (HDL) were observed in the CG and GG genotypes compared to the ADIPOQ rs266729 SNP C.C genotype (p = 0.032). In obese individuals, there was no significant relationship between rs266729 SNP and HbA1C, FBS, TC, and LDL. In conclusion, the single nucleotide polymorphism (rs266729) of the ADIPOQ gene has a significant difference with BMI, insulin, TG, VLDL, and HOMO-IR in obese patients, which might be the cause of obesity.

Association of rs2241766 and rs1501299 polymorphisms in the adiponectin gene with metabolic syndrome.

To investigate the influence of adiponectin (APN) rs2241766 and rs1501299 polymorphisms on adiponectin levels and their association with metabolic syndrome (MetS). Analyzed two polymorphisms (rs2241766 and rs1501299) of the adiponectin gene (ADIPOQ) in 210 MetS patients and 102 control patients using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing technology. The genotypes of the rs2241766 T/G and rs1501299 G/T polymorphism were significantly associated with serum APN levels in MetS patients. The ADIPOQ polymorphisms were associated with a risk of MetS when compared with that in healthy controls. TG and GG genotypes of rs2241766 were associated with a significantly elevated risk of MetS as compared with the TT genotype (OR = 1.32 and OR = 2.53). Subjects with the G allele appeared to have higher susceptibility to MetS than those with the T allele (OR = 2.21). In common with the findings for rs2241766, the rs1501299 GT and TT genotypes were associated with a significantly increased risk of MetS as compared with the GG genotype (OR = 1.51 and OR = 2.24). The susceptibility to MetS appeared to be higher in subjects with the T allele than in those with the G allele (OR = 1.88). The occurrence of MetS may be associated with genetic variations at the rs2241766 and rs1501299 loci, especially in individuals with T to G mutations (rs2241766) and G to T mutations (rs1501299). These mutations may lead to decreased APN levels and a higher risk of developing MetS.

FTO gene polymorphism and susceptibility to polycystic ovary syndrome: A meta-analysis.

To explore the correlation between Fat mass and objectivity associated gene (FTO) rs9939609 polymorphism and susceptibility to polycystic ovary syndrome. Case-control studies on the relationship between FTO rs9939609 A/T polymorphism and PCOS were searched in PubMed, EMBASE, and Web of Science according to inclusion and exclusion criteria. STATA 12.0 software was conducted for Meta-analysis. Nine case-control studies were included, including 1410 cases in PCOS group and 1223 cases in healthy control group. The results of meta-analysis showed that FTO rs9939609 gene polymorphism was associated with PCOS susceptibility, and the risk of developing PCOS was 1.19 times higher for T alleles carriers than for A alleles carriers, and some similar associations were observed in Asian populations. In summary, FTO rs9939609 gene polymorphism is significantly associated with PCOS susceptibility, especially in Asian populations.

Gender-specific associations among neck circumference, the rs9939609 FTO gene polymorphism, and the 14-year risk of metabolic syndrome in the Korean adult population.

Limited data exist on the relation between neck circumference (NC) and the risk of developing metabolic syndrome (MS). This study investigated gender-specific associations between NC and the 14-year risk of MS and explored the impact of the FTO rs9939609 polymorphism on these associations. This population-based prospective cohort study involved 2,666 participants (1,301 men and 1,365 women), who were free of MS at baseline (2005-2006). Incident MS cases, defined by the presence of 3 or more criteria regarding blood pressure and blood levels of glucose, triglycerides, and high-density lipoprotein cholesterol, were identified through biennial examinations until 2020. NC measurements taken at baseline and between 2013 and 2014 were analyzed using Cox proportional hazard regression to determine gender-specific associations with MS risk. Controlling for potential confounders such as waist circumference (WC), significant associations were observed in both genders. Individuals in the highest NC quartile exhibited more than a 2-fold higher MS risk than those in the lowest quartile; with hazard ratios of 2.37 (95% confidence interval [CI], 1.74 to 3.22) for men and 2.65 (95% CI, 1.89 to 3.72) for women (p for trend <0.001). No significant interaction was found between the FTO polymorphism and NC. In diagnostic test analyses, NC and WC demonstrated comparable area under the curve values in both genders. The findings suggest that NC is as effective as WC for predicting the incidence of MS.

Estrogen Receptor-α rs9340799 Polymorphism Influences Bone Mineral Density in Women Over 60 Years of Age and Women Who are Postmenopausal for More than 10 Years

Background: Osteoporosis is a multifactorial disorder where genetic and environmental factors contribute to changes in bone mineral density. Several genetic polymorphisms are associated with low bone mineral density and osteoporosis risk, including estrogen receptor-α rs2234693 and rs9340799 single nucleotide polymorphisms. Objective: To determine the allele frequencies of these polymorphisms among postmenopausal Jordanian women and to assess their association with low bone mineral density and osteoporosis among studied subjects. Methods: This cross-sectional study enrolled 450 postmenopausal Jordanian women having dual-energy X-ray absorptiometry scans at the National Center for Diabetes, Endocrinology, and Genetics. The study protocol was approved by this center "Institutional Review Board." The estrogen receptor-α gene sequence containing rs2234693 and rs9340799 polymorphisms was identified by polymerase chain reaction, followed by restriction fragment length polymorphism. Results: The wild-type allele frequencies of rs2234693 (T) and rs9340799 (A) were 54% and 59%, respectively. The rs9340799 GG genotype was significantly associated with lower femoral neck T-scores in women who were postmenopausal for more than 10 years (p = 0.023) and was significantly associated with lower lumbar spine (p = 0.033) and femoral neck (p = 0.002) T-scores in women older than 60 years of age. However, there was no association between rs2234693, rs9340799, or their haplotypes with osteoporosis or bone mineral density T-score values. The two polymorphisms were in Heidy-Weinberg equilibrium and exhibited strong but incomplete linkage disequilibrium. Conclusion: The data suggest that rs9340799 polymorphism may render some women more susceptible to osteoporosis than others.

A Systematic Review of the Gene-Lifestyle Interactions on Metabolic Disease-Related Outcomes in Arab Populations.

The increased prevalence of metabolic diseases in the Arab countries is mainly associated with genetic susceptibility, lifestyle behaviours, such as physical inactivity, and an unhealthy diet. The objective of this review was to investigate and summarise the findings of the gene-lifestyle interaction studies on metabolic diseases such as obesity and type 2 diabetes in Arab populations. Relevant articles were retrieved from a literature search on PubMed, Web of Science, and Google Scholar starting at the earliest indexing date through to January 2024. Articles that reported an interaction between gene variants and diet or physical activity were included and excluded if no interaction was investigated or if they were conducted among a non-Arab population. In total, five articles were included in this review. To date, among three out of twenty-two Arab populations, fourteen interactions have been found between the FTO rs9939609, TCF7L2 rs7903146, MC4R rs17782313, and MTHFR rs1801133 polymorphisms and diet or physical activity on obesity and type 2 diabetes outcomes. The majority of the reported gene-diet/ gene-physical activity interactions (twelve) appeared only once in the review. Consequently, replication, comparisons, and generalisation of the findings are limited due to the sample size, study designs, dietary assessment tools, statistical analysis, and genetic heterogeneity of the studied sample.

Connection of cirrhosis in the outcome of alcoholic liver disease with the PNPLA3 gene polymorphism rs738409

Connection of cirrhosis in the outcome of alcoholic liver disease with the PNPLA3 gene polymorphism rs738409

Interaction Between FTO rs9939609 Polymorphism and Dietary Inflammatory Index (DII) Affect Prediabetes Risk in Indonesians

Interaction Between FTO rs9939609 Polymorphism and Dietary Inflammatory Index (DII) Affect Prediabetes Risk in Indonesians

The relationship of energy-restricted diet with FTO and MC4R gene polymorphism in patients with polycystic ovary syndrome

Purpose: The aim of this study was to determine whether the effects of an energy-restricted diet on overweight/obese patients with PCOS on body composition and biochemical parameters in groups with MC4R rs17782313 and FTO rs9939609 polymorphisms differ from those without gene polymorphism. Materials and Methods: A total of 48 women aged 18-45 were accepted. An 8-week diet intervention was applied, and anthropometric measurements, biochemical parameters and food consumption of the patients were determined before and after the intervention. In addition, FTO gene rs9939609 and MC4R gene rs17782313 polymorphisms were determined. Results: The incidence of FTO and MC4R gene polymorphism was 72.9% and 68.8% respectively. Change in waist/height ratio was found to be higher in the group without FTO gene polymorphism (-0.03±0.015 cm) compared to the group with gene polymorphism (-0.02 ±0.016 cm). There was no statistically significant difference between the groups with and without MC4R gene polymorphism in terms of change (Δ) in anthropometric measurements. Although not statistically significant, there was a greater decrease in body weight (kg) and BMI (kg/m2) in the group without MC4R gene polymorphism compared to the group with it (without polymorphism group -2.2±1.83 kg; -0.9±0.69 kg/m2). There was no statistically significant difference between the groups with and without gene polymorphism in terms of biochemical parameters. Conclusion: We found that the energy-restricted weight loss diet did not detect a statistically significant change in biochemical parameters in the FTO and MC4R gene polymorphism groups, but the presence of gene polymorphism made it difficult to improve in anthropometric measurements.

Genetic association of FTO gene polymorphisms with obesity and its related phenotypes: A case-control study.

FTO gene belongs to the non-heme Fe (II) and 2 oxoglutarate-dependent dioxygenase superfamily. Polymorphisms within the first intron of the FTO gene have been examined across various populations, yielding disparate findings.The present study aimed to determine the impact of two intronic polymorphisms FTO 30685T/G (rs17817449) and -23525T/A (rs9939609) on the risk of obesity in Punjab, India. Genotypic and biochemical analysis were done for 671 unrelated participants (obese=333 and non-obese=338) (age≥18 years). Genotyping of the polymorphisms was done by PCR-RFLP method. However, 50% of the samples were sequenced by Sanger sequencing. Both the FTO variants 30685 (TT vs GG: odds ratio (OR), 2.30; 95% confidence interval (CI), 1.39-3.79) and -23525 (TT vs AA: odds ratio (OR), 2.78; 95% confidence interval (CI), 1.37-5.64) showed substantial risk towards obesity by conferring it 2 times and 3 times, respectively. The analysis by logistic regression showed a significant association for both the variants 30685T/G (rs17817449) and -23525T/A (rs9939609) (OR=2.29; 95%CI: 1.47-3.57) and (OR=5.25; 95% CI: 2.68-10.28) under the recessive genetic model, respectively. The haplotype combination TA (30685; -23525) develops a 4 times risk for obesity (P=0.0001). Among obese, the G allele of 30685T/G and A- allele of -23525T/A showed variance in Body mass index (BMI), waist circumference (WC), waist-to-height ratio(WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and triglyceride(TG). The present investigation indicated that both the FTO 30685T/G (rs17817449) and -23525T/A (rs9939609) polymorphisms have a key impact on an individual's vulnerability to obesity in this population.

Investigating the Role of Fat Mass and Obesity-Associated (FTO) Single Nucleotide Polymorphisms and Methylation in Breast Cancer.

Background Fat mass and obesity-associated (FTO) protein is an mRNA demethylase enzyme essential for active genome regulation. The FTO gene codes for a protein that is part of the methylosome complex and has a regulatory role in cancer development. Some studies have shown a relationship between FTO and cancer, where single nucleotide polymorphisms (SNPs) may have some impact on cancer risk. The present study aimed to evaluate the risk of FTO polymorphisms rs9939609, rs1477196, and rs9930506; analyze the methylation status of FTO promoters among Mexican women with breast cancer (BC); and investigate by in silico analysis the methylation status in the region near these polymorphisms. Methods A total of 157 BC patients and 137 healthy controls were genotyped for rs9939609, rs1477196, and rs9930506 FTO polymorphisms by TaqMan SNP Genotyping Assays. Promoter methylation was analyzed by sodium bisulfite and methylation-specific polymerase chain reaction (MSP) for 78 tissue samples. An in silico analysis using The Cancer Genome Atlas Program (TCGA) database was employed to investigate the methylation state in promoter and near polymorphism locations and its relation to survival. Results The AG genotype of FTO rs9930506 was associated with BC protection (P= 0.0025; adjusted OR, 0.27; 95% CI: 0.10-0.70). rs9939609 and rs1477196, according to the results of the present study, had no relation to BC. Promoter methylation status assays by MSP revealed no changes in methylation in BC or healthy tissues. Trying to know more about the methylation in promoters and near polymorphisms' relation to survival, we performed an in silico analysis. Bioinformatics analysis showed a correlation between poor survival and methylation near polymorphisms but not with methylation in the promoter region. Conclusions The AG genotype rs9930506 has a protective function against BC. Whereas high methylation near polymorphisms was related to lower survival, the hypomethylated promoter region does not impact survival.