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Evidence for the association between FTO gene variants and vitamin B12 concentrations in an Asian Indian population.

ABSTRACT: Background:Low vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (FTO) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied FTO polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether these associations were modified by dietary factors and physical activity. Methods:A total of 176 individuals with type 2 diabetes, 152 with pre-diabetes, and 220 normal glucose-tolerant individuals were randomly selected from the Chennai Urban Rural Epidemiology Study. Anthropometric, clinical, and biochemical investigations, which included body mass index (BMI), waist circumference, vitamin B12, homocysteine, and folic acid were measured. A validated food frequency questionnaire was used for dietary assessment and self-reported physical activity measures were collected. An unweighted genetic risk score (GRS) was calculated for two FTO single-nucleotide polymorphisms (rs8050136 and rs2388405) by summation of the number of risk alleles for obesity. Interaction analyses were performed by including the interaction terms in the regression model. Results:The GRS was significantly associated with increased BMI (P =?0.009) and risk of obesity (P?=?0.023). Individuals carrying more than one risk allele for the GRS had 13.13% lower vitamin B12 concentrations, compared to individuals carrying zero risk alleles (P?=?0.018). No associations between the GRS and folic acid and homocysteine concentrations were observed. Furthermore, no statistically significant GRS-diet or GRS-physical activity interactions with vitamin B12, folic acid, homocysteine or metabolic-disease outcomes were observed. Conclusion:The study shows for the first time that a genetic risk score using two FTO SNPs is associated with lower vitamin B12 concentrations; however, we did not identify any evidence for the influence of lifestyle factors on this association. Further replication studies in larger cohorts are warranted to investigate the association between the GRS and vitamin B12 concentrations.

SUBMITTER: Surendran S

PROVIDER: S-EPMC6728975 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Evidence for the association between <i>FTO</i> gene variants and vitamin B12 concentrations in an Asian Indian population.

Surendran Shelini S Jayashri Ramamoorthy R Drysdale Lauren L Bodhini Dhanasekaran D Lakshmipriya Nagarajan N Shanthi Rani Coimbatore Subramanian CS Sudha Vasudevan V Lovegrove Julie A JA Anjana Ranjit M RM Mohan Viswanathan V Radha Venkatesan V Pradeepa Rajendra R Vimaleswaran Karani S KS

Genes & nutrition 20190905

<h4>Background</h4>Low vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (<i>FTO</i>) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied <i>FTO</i> polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether t ...[more]

PMID: 31516636

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Project description:BackgroundLifestyle 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).MethodsThe 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.ResultsThere 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)).ConclusionsThis 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.

Dataset Information

Evidence for the association between FTO gene variants and vitamin B12 concentrations in an Asian Indian population.

Publications

Evidence for the association between <i>FTO</i> gene variants and vitamin B12 concentrations in an Asian Indian population.

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