The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women

• We found associations between the MAOA c.1460C > T, COMT c.472G > A, MTHFR c.677C > T and ESR1 454-351 A > G polymorphisms to mild and moderate depressive symptoms in menopausal women.
• No significant differences were observed in either the frequencies of the genotypes or alleles between the patients and the controls in the polymorphic variants of the 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, COMT, NET, GABRB1, MTR and MTHFD1 genes.
• This is an innovative study presenting a new research area and suggesting a direction for further investigation in genetics of depression in women during midlife.

ObjectiveThe aim of the study was assessment of a possible relationship between the polymorphisms of the candidate genes participating in the etiology of some neurological and psychiatric disorders and the risk of depression in perimenopausal and postmenopausal women.MethodsA total of 167 (54 perimenopausal and 113 postmenopausal) Caucasian women from western Poland, aged 42–67, were recruited as the patient group in the study because of depressive symptoms, and another 321 healthy women (102 perimenopausal and 219 postmenopausal) served as the controls. All study participants were evaluated for climacteric and depressive disorders according to the Kupperman index and Hamilton rating scale for depression (HRSD), respectively. The following candidate genes were selected for the study: 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, MAOA, COMT, NET, GABRB1, ESR1, MTHFR, MTR and MTHFD1. In each group the frequencies of the polymorphisms were determined using PCR-RFLP analysis.ResultsAfter correcting for Bonferroni multiple tests, we found associations between the MAOA c.1460C > T (SNP 1137070), COMT c.472G > A (SNP 4680), MTHFR c.677C > T (SNP 1801133) and ESR1 454−351 A > G (SNP 9340799) polymorphisms to mild and moderate depressive symptoms in menopausal women. In the perimenopausal and postmenopausal women, genotype association of the MAOA c.1460 CT and c.1460 CT + TT (OR = 1.83; pcorr = 0.009 and OR = 1.85; pcorr = 0.003, resp.), and of the MTHFR c.677 TT and c.677 CT + TT (OR = 3.52; pcorr = 0.00009 and OR = 2.06; pcorr = 0.0006, resp.), as well as of the COMT c.472 GA and COMT c.472 GA + AA genotypes (OR = 2.23; pcorr = 0.03 and OR = 2.17; pcorr = 0.027, resp.) in the postmenopausal women revealed significantly higher frequencies of these variants in depressed female patients than in controls, whereas the ESR1 454−351 AG and 454−351 AG + GG genotypes were associated with lower risk of depression in postmenopausal women (OR = 0.48; pcorr = 0.012, and OR = 0.52; pcorr = 0.015, resp.).ConclusionsOur study substantiates the involvement of the MAOA and MTHFR polymorphisms in climacteric depression and offers evidence that the COMT and ESR1 genes may also play a role in the susceptibility to depressive mood in postmenopausal women.