The genetic background of climacteric symptoms in women during menopause.

The subject of the study is the evaluation of the correlation between the polymorphism of candidate genes in the etiology of depression and the occurrence of the symptoms of the climacteric syndrome in women during menopause. The group subjected to the study comprised of 203 women aged between 42-65 years: 71 of them still menstruated (premenopausal group) and 132 at least one year after the last period (postmenopausal group), admitted to the Department of Gynecological Endocrinology at the University of Medical Sciences in Poznan with symptoms of the climacteric syndrome All the examined women were evaluated according to the degree of severity of the climacteric syndrome symptoms using the Kupperman index and the concentration of FSH, LH hormones, 17ß-estradiol, PRL, total testosterone, and DHEAS in peripheral blood serum. Among the candidate genes in the aetiology of depression the following were selected for the research: the serotonergic system receptor genes: 5HTR2A, 5HTR1B, 5HTR2C, TPH 1, TPH2, and MAO-A; the genes of noradrenergic and dopaminergic systems (COMT, NET), the genes of the GABAergic (GABRBl) system, a gene of the estrogen receptor (ESR1), and the genes of the enzymes crucial in the methyl cycle (MTHRF, MTR, and MTHFD1). With regards to the correlation between the examined polymorphisms and the occurrence of the symptoms of the climacteric syndrome, the associations analysis indicated a connection between GABRBl.TaqI polymorphism and the occurrence of vertigo in premenopausal women (0.0198; after correction: 0.0497 CC to CA). The correlation was also found regarding the examined polymorphisms and the concentration of the examined hormones in blood serum: TPH1.MaeI polymorphism and the LH concentration in the postmenopausal group (0.004; after correction: 0.014 CC to CA), NET.Eco1471 polymorphism, and the 17ß-estradiol concentration in the postmenopausal group (0.0208; after correction: 0.048 GG to GA) and HTR2AMspI polymorphism and PRL concentration in all examined women (0.03; after correction: 0.038 TT to CT).

The c.1460C>T polymorphism of MAO-A is associated with the risk of depression in postmenopausal women.

OBJECTIVE: The aim of the study was an evaluation of possible relationships between polymorphisms of serotoninergic system genes and the risk of depression in postmenopausal women. METHODS: We studied 332 women admitted to our department because of climacteric symptoms. The study group included 113 women with a diagnosis of depressive disorder according to the Hamilton rating scale for depression; the controls consisted of 219 women without depression. Serum 17ß-estradiol concentrations were evaluated using radioimmunoassay, while polymorphisms in serotoninergic system genes: serotonin receptors 2A (HTR2A), 1B (HTR1B), and 2C (HTR2C); tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), and monoamine oxidase A (MAO-A) were evaluated using polymerase chain reaction-restriction. RESULTS: We found that the 1460T allele of MAO-A c.1460C>T (SNP 1137070) appeared with a significantly higher frequency in depressed female patients than in the control group (P = 0.011) and the combined c.1460CT + TT genotypes were associated with a higher risk of depression (P = 0.0198). Patients with the 1460TT genotype had a significantly higher 17ß-estradiol concentration than patients with the 1460CT genotype (P = 0.0065) and 1460CC genotype (P = 0.0018). CONCLUSIONS: We concluded that depression in postmenopausal women is closely related to the genetic contribution of MAO-A.