The methylenetetrahydrofolate reductase C677T genotype and the risk of obesity in three large population-based cohorts

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.