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FTO-rs9939609 Polymorphism is a Predictor of Future Type 2 Diabetes: A Population-Based Prospective Study.

ABSTRACT: The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective study included 1443 nondiabetic subjects at baseline, and they were examined for developing T2D after 5-year follow-up. Cox proportional hazards model was used to evaluate the hazard ratio (HR) of rs9939609 to the future T2D in the models adjusted for the confounding factors including socio-economic status, lifestyle factors (smoking and drinking history, sporting habits, and leisure time), and clinical patterns (obese status, blood pressures, and dyslipidemia) at baseline. The area under receiver operating characteristic curve (AUC) was used to measure the power to predict individuals with T2D. The FTO-rs9939609 polymorphism was a significant predictor of future T2D in the model unadjusted, and it remained significant in the final model after adjustment for the confounding factors, showing an additive effect of the A-allele (HR = 1.35, 95% CI = 1.02-1.78, P = 0.036, AUC = 0.676). For normoglycemic subjects at baseline, the similar final adjusted model reported the increased HR per A-allele (HR = 1.50, 95% CI = 1.09-2.07, P = 0.012, AUC = 0.697). Five-year changes in BMI, waist circumference, and systolic blood pressure did not remove the contribution of rs9939609 to increased HR of T2D. The population attributable risk for risk genotype was 13.6%. In conclusion, the study indicates that the FTO-rs9939609 polymorphism is an important genetic predictor for future T2D in Vietnamese population.

SUBMITTER: Binh TQ

PROVIDER: S-EPMC8375613 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsObesity is a growing public health concern in Bangladesh, which is influenced by a complex interplay of genetic and environmental factors. The genetic variant rs9939609 of the FTO (fat mass and obesity-associated) gene has been found to be associated with an increased risk for obesity, depending on the population studied. The purpose of this cross-sectional study is to examine the relationship between the FTO gene polymorphism (rs9939609) and lifestyle-related risk factors, and their impact on obesity-related traits and biochemical parameters in the Bangladeshi population.MethodsA total of 280 participants were enrolled in this study, comprising of 140 individuals with overweight and obesity (body mass index [BMI] ≥ 23.0) and 140 non-overweight healthy individuals (18.5 ≤ BMI ≥ 22.9). Demographic information, dietary behaviors, and physical activity-related data were collected using a structured questionnaire. Additionally, anthropometric assessments and measurements of biochemical parameters such as lipid profile and C-reactive protein were performed. The amplification refractory mutation system-polymerase chain reaction technique was used to identify single-nucleotide polymorphism in the FTO gene. Descriptive statistics, χ,2 and one-way ANOVA were performed to evaluate the relationships between independent and dependent variables.ResultsThe presence of rs9939609 was strongly associated with the obesity risk factors of increased BMI, cholesterol, triglycerides, and low-density lipoprotein. We also found a significant association (p < 0.05) of rs9939609 with overweight and obesity in codominant AA versus TT (odds ratio [OR] = 0.299, 95% CI: 0.129-0.695) and AA versus AT (OR = 2.273, 95% CI: 1.023-5.053), recessive TT versus AA+AT (OR = 5.154, 95% CI: 2.463-10.782), and overdominant AT versus AA+TT (OR = 0.244, 95% CI: 0.122-0.488) models.ConclusionFTO variant rs9939609 is significantly linked to obesity and an increased risk of hyperlipidemia in the Bangladeshi population. However, this association is intertwined with environmental factors such as diet and physical activity.

Project description:BackgroundThe role of inflammatory states in cardiometabolic risks among patients with type 2 diabetes mellitus (T2DM) with similar degrees of obesity is unknown. The study aimed to compare cardiometabolic risk factors in inflammatory obesity phenotypes with regard to the role of the FTO rs9939609 gene polymorphism.Materials and methodsThis study was performed on 155 patients with T2DM (77 men and 78 women) in Ahvaz, Iran. Participants were grouped into four groups based on the presence of obesity and inflammation (high-sensitivity C-reactive protein ≥3.9 mg/L): low inflammatory normal weight (LINW), high inflammatory normal weight (HINW), low inflammatory obese (LIO), and high inflammatory obese (HIO). The genotypes of FTO rs9939609, including homozygous carriers of the FTO risk allele (AA), heterozygous carriers (AT), and carrying no risk allele (TT), were studied. The cardiometabolic risk factors, including anthropometric status, hypertension, lipid and glycemic profile, and inflammatory markers, were evaluated. The waist-hip ratio (WHR), mean arterial pressure (MAP), and atherogenic index of plasma (AIP) were calculated.ResultsThe patients in inflammatory groups (HINW and HIO) have significantly higher levels in AIP when compared to inflammatory healthy groups (LINW and LIO). No significant differences between any of the four group means were detected in WHR, blood pressure, MAP, glycemic status (fasting blood sugar and insulin), homeostatic model assessment, lipid profile (triglyceride, very low-density lipoprotein, high-density lipoprotein, low-density lipoprotein, and cholesterol), interleukin-6, and total antioxidant capacity. The most frequent of high-risk genotype (AA) of FTO rs9939609 was in HIO, LIO, HINW, and LINW.ConclusionT2DM patients with inflammatory condition have similar degree of increased atherogenic risk irrespective of obesity. The obesity-risk genotype AA of FTO gene was associated with an increased risk for inflammatory obesity in T2DM patients.

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FTO-rs9939609 Polymorphism is a Predictor of Future Type 2 Diabetes: A Population-Based Prospective Study.

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