Polymorphisms in vitamin B12 and folate metabolising genes and their association with adverse pregnancy outcome: secondary analysis of a population based case control study.

Vitamin B12 and folate deficiency leads to accumulation of homocysteine that increases the risk of adverse pregnancy outcomes like preterm birth and low birth weight (LBW) of the neonate. We explored the association of genetic variants of key vitamin B12 and folate metabolising enzymes (MTHFR C677T and A1298C, MTR A2756G, TCN-2 C776G) with preterm birth and LBW in South Indian women. MTHFR A1298C heterozygotes (AC) were at higher risk for preterm delivery, whereas TCN-2 C776G heterozygotes (CG) were at higher risk for both preterm delivery and LBW. MTHFR C677T, A1298C and MTR A2756G haplotype CAG was protective for preterm delivery (p=.036, OR = 0.475; 95% CI: 0.233-0.97), whereas, haplotype CCG increasing the risk of preterm birth by 1.8 folds (p=.018, OR = 1.81; 95% CI: 1.09-2.98). These results underscore the significance of vitamin B12 and folate in the pathophysiology of preterm birth and LBW.Impact StatementWhat is already known on this subject? Polymorphisms of vitamin B12 and folate metabolising genes have been reported to influence preterm birth and LBW, but the reports are not consistent.What do the results of this study add? We observed a relationship of MTHFR A1298C and TCN-2 C776G with preterm birth, and significant association of TCN-2 C776G with LBW in infants.What are the implications of these findings for clinical practice and/or further research? Identification of women carrying these polymorphic risk alleles may benefit from early nutritional modifications.