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


METHODS
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).


RESULTS
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).


CONCLUSIONS
Our findings indicate a significant role of folate and possible methionine metabolism involvement in the development of depression in postmenopausal women.
Słopien
R
R
Department of Gynecological Endocrinology, Poznań University of Medical Sciences, 6 Swiecickiego Street, 60-781 Poznan, Poland. asrs@wp.pl
Jasniewicz
K
K
Meczekalski
B
B
Warenik-Szymankiewicz
A
A
Lianeri
M
M
Jagodziński
P P
PP
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000368:Aged; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003863:Depression / Q000201:enzymology / Q000235:genetics* / Q000523:psychology; D005260:Female; D005574:Formate-Tetrahydrofolate Ligase / Q000235:genetics; D005838:Genotype; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011044:Poland; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics* / Q000523:psychology
D004247:DNA; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D005574:Formate-Tetrahydrofolate Ligase