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Fat mass and obesity-associated gene rs11642015 polymorphism is significantly associated with prediabetes and type 2 diabetes subsequent to adjustment for body mass index.

ABSTRACT: The association of the fat mass and obesity-associated gene (FTO) rs11642015 polymorphism with prediabetes, type 2 diabetes and obesity in certain populations has not been previously reported. A population-based study was conducted that included 490 type 2 diabetic, 471 prediabetic and 575 normal subjects. The main outcomes of the study were prediabetes, type 2 diabetes and obesity. Binary logistic regression was performed to estimate the association of FTO rs11642015 with the risk of prediabetes, type 2 diabetes and obesity following adjustment for the corresponding confounders. A meta-analysis was also conducted to evaluate the association between FTO rs11642015 and obesity. FTO rs11642015 was significantly associated with prediabetes in the whole sample under the additive model [odds ratio (OR), 1.50; 95% confidence interval (CI), 1.17-1.93; P=0.002], particularly in females. The polymorphism remained consistently significant following adjustment for age and body mass index (BMI), showing an increased prediabetes risk with an additive effect (OR, 1.55; 95% CI, 1.19-2.01; P=0.001). In addition, a significant association was found for rs11642015 with prediabetes and type 2 diabetes under the dominant model. However, under the stringent Bonferroni's correction there was no evidence of positive associations for FTO rs11642015 with obesity in the whole sample, females or males. Findings of the meta-analysis showed that FTO rs11642015 was not predisposed to obesity. In conclusion, the T allele of FTO rs11642015 is positively associated with an increased risk of prediabetes, even after adjustment for age and BMI, particularly in females. Subjects carrying the CT + TT genotype are predisposed to prediabetes and type 2 diabetes. Therefore, results of the population-based study and follow-up meta-analysis suggested that FTO rs11642015 is not significantly associated with susceptibility to obesity.

SUBMITTER: Han L

PROVIDER: S-EPMC4106513 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Fat mass and obesity-associated gene rs11642015 polymorphism is significantly associated with prediabetes and type 2 diabetes subsequent to adjustment for body mass index.

Han Liyuan L Tang Linlin L Wang Changyi C Chen Zhongwei Z Zhang Tao T Chen Sihan S Liu Shengyuan S Peng Xiaolin X Mai Yifeng Y Duan Shiwei S

Biomedical reports 20140526 5

The association of the fat mass and obesity-associated gene (<i>FTO</i>) rs11642015 polymorphism with prediabetes, type 2 diabetes and obesity in certain populations has not been previously reported. A population-based study was conducted that included 490 type 2 diabetic, 471 prediabetic and 575 normal subjects. The main outcomes of the study were prediabetes, type 2 diabetes and obesity. Binary logistic regression was performed to estimate the association of <i>FTO</i> rs11642015 with the risk ...[more]

PMID: 25054011

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Project description:A single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is a strong predictor of obesity in humans. The FTO SNP (rs1421085) results in a T to C nucleotide substitution that may result in an increased risk for obesity in individuals who carry at least one C allele. The purpose of this investigation was to characterize the FTO genotype in a cohort of exercise-trained men and women.We tested 108 exercise-trained individuals that included professional mixed martial arts fighters, competitive distance runners, collegiate swimmers, stand-up paddlers as well as a cohort of recreational bodybuilders. Body composition was assessed via dual-energy x-ray absorptiometry (DXA). Saliva samples were collected in order to genotype participants and quantify cortisol levels.The physical characteristics of the subjects were as follows (mean±SD): body weight 74.5±15.6 kg; height 171.5±9.5 cm; bone mineral content 2.8±0.7 kg; fat mass 15.7±5.5 kg; lean body mass 55.9±14.4 kg; % body fat 21.6±7.0. Independent samples t tests showed that C allele carriers (n =?54) had significantly higher fat mass t(106)?=?3.13, p <?0.01 and body fat percentage t(106)?=?2.68, p?<?0.01, relative to the TT group (n?=?54) (i.e., fat mass: C/-?17.3 ±5.6 kg, TT 14.2±4.6 kg; body fat percentage: C/- group 23.4±7.4%, TT group 19.9±6.2). No other measures of body composition were associated with the FTO genotype (i.e., body mineral density, bone mineral content, or lean body mass). Moreover, cortisol levels were significantly higher in the TT group relative to the C allele carriers t(106)?=?2.37, p =?0.02 (i.e., TT 0.35 ±0.35 ?g/dL, C/-?0.22±0.16 ?g/dL).Our findings demonstrate a relationship between C allele carriers on the FTO gene and a predisposition to a higher fat mass and body fat percentage. In addition, we found no relationship between cortisol and fat mass. However, due to the cross-sectional nature of this investigation, we cannot infer causality regarding the FTO gene and body composition.

Project description:BackgroundAccurate obesity classification is important so that appropriate intervention can be instituted to modify metabolic risk factors. Commonly utilized body mass index (BMI) and percentage body fat (PBF) are influenced by lean mass whereas fat mass index (FMI) measures only body fat. This study compares the prevalence of obesity and metabolic risk factors with FMI, BMI and PBF using DXA (dual-energy x-ray absorptiometry).Methods489 women randomly recruited from the electoral roll were stratified into 4 age groups; 40-49, 50-59, 60-69 and 70-79 years from 2000 to 2001. Clinical data and DXA body composition were obtained. Statistical analyses were performed using Medcalc v15 (Ostend, Belgium) with significance level at p = 0.05 (two-tailed).ResultsThere was higher prevalence of obesity using PBF compared to BMI and FMI (p<0.001). This difference was greater from age 50-59 (p<0.05) which may be explained by age-related lean mass loss. PBF over-classified obesity in over 35% of normal and 95% of overweight categories compared to FMI and BMI. BMI has a sensitivity of 78.9% and specificity of 98.3% for obesity using FMI as the standard. BMI under-classified obesity in the overweight category by 14.9% compared to FMI. There was no difference in diabetes, dyslipidemia, hypertension and metabolic syndrome prevalence within the BMI-obesity and FMI-obesity categories (p>0.05).ConclusionPBF classified more obesity than BMI and FMI because of its low pre-determined threshold. The greater difference with PBF compared to BMI and FMI from the 50-59 decade onwards can be attributed to age-related lean mass loss. BMI had the lowest sensitivity for obesity diagnosis. BMI under-classified obesity in the overweight category compared to FMI due to its inability to differentiate lean mass. However, there was no significant difference in the prevalence of metabolic risk factors between BMI and FMI-obesity categories indicating that fat location may influence metabolic dysregulation.

Dataset Information

Fat mass and obesity-associated gene rs11642015 polymorphism is significantly associated with prediabetes and type 2 diabetes subsequent to adjustment for body mass index.

Publications

Fat mass and obesity-associated gene rs11642015 polymorphism is significantly associated with prediabetes and type 2 diabetes subsequent to adjustment for body mass index.

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