Polymorphisms of Methylene Tetrahydrofolate Reductase (MTHFRC677T and A1298C) and Probable Depression in Postpartum Period in South Indian Women

Background: Two common variants of Methylene tetrahydrofolate reductase ( MTHFR ) are C677T and A1298C, which have been associated with general depression. Main objective of the study was to explore how these functional polymorphisms of MTHFR gene associate with the risk to develop postpartum depression. Method: 434 women were recruited in a study period of 3 years (January 2014 to December 2017) in a tertiary care centre. EPDS was administered at 6 weeks postpartum, with a cut-off score of ≥10 to define probable postpartum depression. Plasma was used for the estimation of circulating vitamin B12 metabolites and whole blood for extraction of DNA. Real time PCR using Taqman probes was used for genotyping the proposed SNP’s. Results: T allele of MTHFR C677T was associated with the risk of probable PPD (p = 0.024, OR = 1.67; 95% CI: 1.06-2.62) and presence of suicidal ideations in these women (p<0.001, OR = 2.90; 95% CI: 1.61-5.24). Haplotype 677T-1298A was associated with both the risk of probable PPD (p = 0.029, OR = 1.66; 95% CI: 1.05-2.64) and suicidal ideations (p <0.001, OR = 2.933; 95% CI: 1.60-5.35), whereas 677C-1298A was protective against suicidal ideations (p = 0.011; OR = 0.558; 95% CI: 0.35-0.88). Women with risk allele T were also associated with higher levels of circulating holotranscobalamin levels, and lower levels of vitamin B12, whereas risk allele C of A1298C had lower levels of holotranscobalamin. Limitations: Cross-sectional studyConclusion: Polymorphic variants of MTHFR gene might indicate susceptibility to develop probable depression in postpartum period. Significance MTHFR C677T has been widely reported in the literature to be associated with general depression. The association of this variant in susceptibility to develop postpartum depression is not widely studied. We observed T allele of MTHFR C677T to be associated with the risk of to develop depression and suicidal ideation in postpartum period. Higher levels of MMA and holotranscobalamin, and lower levels of vitamin B12 were associated with T allele of MTHFR C677T. Polymorphic variants of MTHFR gene might indicate susceptibility to develop depression in postpartum period.