Polymorphic variants of genes encoding MTHFR, MTR, and MTHFD1 and the risk of depression in postmenopausal women in Poland.

Disturbances in the folate-dependent one-carbon metabolism have been reported in depression. Polymorphic variants of genes encoding key enzymes of folate and methionine metabolism may have an impact on catecholamine catabolism conducted by catechol-O-methyltransferase. The distribution of polymorphisms of genes encoding methylenetetrahydrofolate reductase (MTHFR); methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1) was examined in postmenopausal women with (n=83) and without depression (n=89). We found a significant contribution of the MTHFR 677C>T polymorphic variants to depression in postmenopausal women. Odds ratio (OR) for women with depression and MTHFR TT genotype was 3.478 (95% CI=1.377-8.783), P=0.0096 and OR of the TT and CT genotypes was 2.345 (95% CI=1.258-4.373), P=0.0086. Moreover, after stratification based on depression severity in postmenopausal women, we found that the MTHFR TT genotype displayed a 4.831-fold increased risk of moderate and severe depression (95% CI=1.975-11.820, P=0.0008). We did not observe statistical differences in the distribution of MTR 2756A>G and MTHFD1 1958G>A polymorphic variants in groups of postmenopausal women with and without depression. However, the MTR GG genotype exhibited a 5.750-fold increased risk of moderate and severe depression in postmenopausal women (95% CI=1.547-21.379, P=0.013). Our findings indicate a significant role of folate and possible methionine metabolism involvement in the development of depression in postmenopausal women.