Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population.
BACKGROUND
Lifestyle factors such as diet and physical activity have been shown to modify the association between fat mass and obesity-associated (FTO) gene variants and metabolic traits in several populations; however, there are no gene-lifestyle interaction studies, to date, among Asian Indians living in India. In this study, we examined whether dietary factors and physical activity modified the association between two FTO single nucleotide polymorphisms (rs8050136 and rs11076023) (SNPs) and obesity traits and type 2 diabetes (T2D).


METHODS
The study included 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the urban component of the Chennai Urban Rural Epidemiology Study (CURES). Dietary intakes were assessed using a validated interviewer administered semi-quantitative food frequency questionnaire (FFQ). Physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the linear/logistic regression model.


RESULTS
There was a significant interaction between SNP rs8050136 and carbohydrate intake (% energy) (Pinteraction = 0.04), where the 'A' allele carriers had 2.46 times increased risk of obesity than those with 'CC' genotype (P = 3.0 × 10(-5)) among individuals in the highest tertile of carbohydrate intake (% energy, 71 %). A significant interaction was also observed between SNP rs11076023 and dietary fibre intake (Pinteraction = 0.0008), where individuals with AA genotype who are in the 3(rd) tertile of dietary fibre intake had 1.62 cm lower waist circumference than those with 'T' allele carriers (P = 0.02). Furthermore, among those who were physically inactive, the 'A' allele carriers of the SNP rs8050136 had 1.89 times increased risk of obesity than those with 'CC' genotype (P = 4.0 × 10(-5)).


CONCLUSIONS
This is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. Our findings suggest that the association between FTO SNPs and obesity might be influenced by carbohydrate and dietary fibre intake and physical inactivity. Further understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions is warranted to advance the development of behavioral intervention and personalised lifestyle strategies, which could reduce the risk of metabolic diseases in this Asian Indian population.
Hugh Sinclair Unit of Human Nutrition and Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading, UK.
Karani S
KS
Vimaleswaran
Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, India.
Dhanasekaran
D
Bodhini
Department of Foods, Nutrition and Dietetics Research, Madras Diabetes Research Foundation, Chennai, India.
N
N
Lakshmipriya
Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, India.
K
K
Ramya
Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, India ; Department of Foods, Nutrition and Dietetics Research, Madras Diabetes Research Foundation, Chennai, India ; Dr. Mohan's Diabetes Specialties Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, Chennai, India.
R Mohan
RM
Anjana
Department of Foods, Nutrition and Dietetics Research, Madras Diabetes Research Foundation, Chennai, India.
Vasudevan
V
Sudha
Hugh Sinclair Unit of Human Nutrition and Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading, UK.
Julie A
JA
Lovegrove
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Sanjay
S
Kinra
Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, India ; Department of Foods, Nutrition and Dietetics Research, Madras Diabetes Research Foundation, Chennai, India ; Dr. Mohan's Diabetes Specialties Centre, WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, Chennai, India.
Viswanathan
V
Mohan
Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, India.
Venkatesan
V
Radha
Asian Indian; BMI; CURES; Carbohydrate intake; Dietary fibre; FTO gene variant; Obesity; Physical activity; Type 2 diabetes