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The MTHFR C677T genotype and the risk of obesity in 3 large population based cohorts

S Lewis, Social Medicine, University of Bristol, Bristol, BS8 2PR, United Kingdom
D Lawlor, Bristol, United Kingdom
B Nordestgaard, Copenhagen, Denmark
A Tybjaerg-Hansen, Copenhagen, Denmark
S Ebrahim, London, United Kingdom
J Zacho, Copenhagen, Denmark
A Ness, Bristol, United Kingdom
S Leary, Bristol, United Kingdom
G Davey-Smith, Canynge Hall, Dept Social Medicine, Bristol, United Kingdom

Correspondence: Sarah Lewis, Email: s.j.lewis{at}bristol.ac.uk

Abstract

Objective: Epidemiological studies have shown that low folate levels are associated with a high body mass index. These findings have potentially important health implications and warrant further investigation to determine whether a causal relationship exists and the direction of this relationship. The MTHFR C677T TT genotype, is associated with reduced folate availability and may be a surrogate for measuring folate levels. We sought to determine whether the MTHFR C677T genotype was associated with obesity.

Design; We carried-out our study on 4 populations from 3 longitudinal studies based in the UK and Denmark in which DNA for genotyping was obtained along with measures of obesity.

Methods: Our subjects were taken from; The British Womens Heart and Health Study, the Avon Longitudinal Study of Parents and Children (2 populations: mothers and children) and the Copenhagen City Heart Study. We performed analyses separately by population, and then carried out a meta-analysis, combining similar populations.

Results: Initial findings in the BWHHS suggested that the TT genotype may be associated with an increased risk of obesity (BMI > or = 30), however no association was found with BMI or central adiposity in this cohort. This genotype was not associated with obesity in our other cohorts.

Conclusions: Our results suggests that the initial positive finding with obesity in the BWHHS was a chance finding. Our findings do not support a causal effect of low folate on obesity.