Association of MTHFR C677T Polymorphism With Recurrent Pregnancy Loss in a South Indian Population

Abstract

The C677T variant of the methylenetetrahydrofolate reductase gene (MTHFR) is one of the most studied candidate polymorphisms in reproductive genetics. It lowers the stability and activity of an enzyme at the centre of folate metabolism, and it has been proposed as a risk factor for recurrent pregnancy loss through raised homocysteine and disturbed methylation. This narrative review sets out what the published literature says about that proposal and how firmly it can be held. It draws on work on folate and homocysteine biochemistry, on the definition and causes of recurrent pregnancy loss, and on case-control studies, meta-analyses and the methodological literature on genetic association, and it reports no new data; the title s reference to a South Indian population is treated as a setting for the question, and no local data are presented. The biological case is plausible, and the effect of the variant on homocysteine is clearest where folate intake is low. The epidemiological case is less settled: summary estimates from pooled studies point to a modest association in some populations and none in others, and between-study heterogeneity, small samples, loosely defined cases and uncontrolled population structure weaken most individual reports. Routine testing of the variant is not supported by professional guidance. The review closes with the design features that a convincing study in this setting would need.