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

¹ Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK² MRC Centre for Causal Analyses in Translational Epidemiology,, University of Bristol, Bristol, UK³ Department of Clinical Biochemistry,, Herlev University Hospital⁴ The Copenhagen City Heart Study,, Bispebjerg University Hospital and ⁵ Department of Clinical Biochemistry,, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark⁶ Department of Epidemiology and Population Health,, London School of Hygiene and Tropical Medicine, London, UK and ⁷ Department of Oral and Dental Science,, University of Bristol, Bristol, UK

(Correspondence should be addressed to S Lewis; Email: s.j.lewis{at}bristol.ac.uk)

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 BMI30, 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.