Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism on blood folate concentrations: a systematic review and meta‐analysis of trials and observational studies (LB311)

Abstract

Background: The methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism is a risk factor for neural tube birth defects (NTDs). The T allele produces an enzyme with reduced folate processing capacity, which has been shown to produce lower blood folate concentrations in some studies.Objective: To assess the association between MTHFR C677T genotypes (CC, CT, TT) and blood folate concentrations among women aged 12‐49 years.Design: We conducted a systematic review of literature published between 1/1992‐7/2013 to identify controlled trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We applied a Bayesian random‐effects model to predict differences in blood folate concentrations between MTHFR C677T genotypes, stratified by folate assay.Results: Thirty‐eight studies met criteria for inclusion. Serum/plasma folate concentrations showed a consistent genotype trend with the highest concentrations for CC (CC > CT > TT) regardless of assay type. RBC folate concentrations measured by microbiologic assay also demonstrated this trend; however, this trend was reversed (CC < CT < TT) in studies using protein‐binding assays.Conclusions: Meta‐analyses results showed blood folate concentrations differed by assay type and genotype. Previous evidence has shown that RBC folate concentrations measured with a radioimmunoassay requires adjustment for genotype‐dependent folate recovery; our results suggest that other protein‐binding assays could have similar limitations. Compared to CC individuals, TT individuals have lower blood folate concentrations, which may increase a woman’s risk for an NTD‐affected pregnancy.