Genetic polymorphisms of vitamin B12 and folate transporter proteins and depression in postpartum period: A case-control study

Abstract

• First study to explore association of vitamin B12 and folate transporter protein polymorphisms (TCN-2 C776G and RFC-1 G80A) with depression in postpartum period. • No association was observed between TCN-2 C776G and RFC-1 G80A & postpartum. • TCN2 C776G CG genotype was associated with lower 5-methylTHF and SAM levels. • RFC-1 G80A GA genotype was associated with lower vitamin B12 levels. • Observations suggest the role of transporter genotype on vitamin B12 and folate homoeostasis. Vitamin B12 and folate deficiency have been linked to the susceptibility of developing depression in the postpartum period. Transcobalamin-2 (TCN-2) and reduced folate carrier (RFC-1) are essential for the cellular uptake of vitamin B12 and folate respectively. Therefore, functional genetic polymorphism of both may lead to the intracellular deficiency of vitamin B12 & folate. We observed the association of TCN-2 C776G and RFC-1 G80A polymorphism with postpartum depression, and its effect on the circulating markers of vitamin B12 and folate deficiency. Women were screened at 6 weeks postpartum for the probability of depression by EPDS score, and a score of >10 was taken as a cut-off ( n = 434; 217 in each group). Plasma was used for the estimation of homocysteine, methylmalonic acid (MMA), 5-methyl tetrahydrofolate, and holotranscobalamin by commercially available ELISA kits, and whole blood was used for extraction of DNA, which was further genotyped by real-time PCR using Taqman probes. No difference was observed between the distribution of genotypes and alleles of TCN-2 C776G and RFC-1 G80A between women with and without probable depression. On comparing the effect of various genotypes on circulating levels of metabolites, we observed TCN2 C776G CG genotype to be associated with lower 5-methyl THF levels whereas RFC-1 G80A GA genotype was associated with lower vitamin B12 levels. These results suggest the metabolic effect of transporter genotype in folate-supplemented postpartum women.