Słopien R, Jasniewicz K, Meczekalski B, Warenik-Szymankiewicz A, Lianeri M, Jagodziński P P
Department of Gynecological Endocrinology, Poznań University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznan, Poland.
Maturitas. 2008 Nov 20;61(3):252-5. doi: 10.1016/j.maturitas.2008.08.002. Epub 2008 Sep 17.
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.
据报道，抑郁症患者存在叶酸依赖性一碳代谢紊乱。编码叶酸和甲硫氨酸代谢关键酶的基因多态性变异可能会影响儿茶酚-O-甲基转移酶介导的儿茶酚胺分解代谢。
检测了患有（n = 83）和未患有抑郁症（n = 89）的绝经后女性中，编码亚甲基四氢叶酸还原酶（MTHFR）、甲硫氨酸合成酶（MTR）、5,10-亚甲基四氢叶酸脱氢酶、5,10-亚甲基四氢叶酸环水解酶和10-甲酰四氢叶酸合成酶（MTHFD1）的基因多态性分布。
我们发现MTHFR 677C>T多态性变异对绝经后女性抑郁症有显著影响。患有抑郁症且为MTHFR TT基因型的女性的优势比（OR）为3.478（95%置信区间=1.377 - 8.783），P = 0.0096；TT和CT基因型的OR为2.345（95%置信区间=1.258 - 4.373），P = 0.0086。此外，在根据绝经后女性抑郁症严重程度分层后，我们发现MTHFR TT基因型显示中度和重度抑郁症风险增加4.831倍（95%置信区间=1.975 - 11.820），P = 0.0008。我们未观察到患有和未患有抑郁症的绝经后女性组中MTR 2756A>G和MTHFD1 1958G>A多态性变异分布的统计学差异。然而，MTR GG基因型在绝经后女性中显示中度和重度抑郁症风险增加5.750倍（95%置信区间=1.547 - 21.379），P = 0.013。
我们的研究结果表明叶酸以及可能的甲硫氨酸代谢在绝经后女性抑郁症的发生发展中起重要作用。
