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

Abstract

Objective

Epidemiological studies have shown that low folate levels are associated with a high body mass index (BMI). 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 methylenetetrahydrofolate reductase ( MTHFR) C677T TT genotype is associated with reduced folate availability and may be a surrogate for measuring folate levels. We sought to determine whether MTHFR C677T genotype was associated with obesity.

Design

We carried out our study on four populations from three 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 Women's Heart and Health Study (BWHHS), the Avon Longitudinal Study of Parents and Children (two 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≥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 suggest 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.