Różycka Agata, Słopień Radosław, Słopień Agnieszka, Dorszewska Jolanta, Seremak-Mrozikiewicz Agnieszka, Lianeri Margarita, Maciukiewicz Małgorzata, Warenik-Szymankiewicz Alina, Grzelak Teresa, Kurzawińska Grażyna, Drews Krzysztof, Klejewski Andrzej, Jagodziński Paweł P
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
Maturitas. 2016 Feb;84:42-54. doi: 10.1016/j.maturitas.2015.10.011. Epub 2015 Oct 30.
The 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.
A 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.
After 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.).
Our 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.
本研究旨在评估参与某些神经和精神疾病病因的候选基因多态性与围绝经期和绝经后女性抑郁症风险之间的可能关系。
从波兰西部招募了167名（54名围绝经期和113名绝经后）年龄在42 - 67岁的白人女性作为研究中的患者组，她们因抑郁症状入选，另外321名健康女性（102名围绝经期和219名绝经后）作为对照组。所有研究参与者分别根据库珀曼指数和汉密尔顿抑郁评定量表（HRSD）评估更年期和抑郁障碍。选择以下候选基因进行研究：5HTR2A、5HTR1B、5HTR2C、TPH1、TPH2、MAOA、COMT、NET、GABRB1、ESR1、MTHFR、MTR和MTHFD1。在每组中，使用聚合酶链反应 - 限制性片段长度多态性分析（PCR - RFLP）确定多态性的频率。
在进行Bonferroni多重检验校正后，我们发现MAOA基因c.1460C>T（SNP 1137070）、COMT基因c.472G>A（SNP 4680）、MTHFR基因c.677C>T（SNP 1801133）和ESR1基因454(-351)A>G（SNP 9340799）多态性与绝经后女性的轻度和中度抑郁症状之间存在关联。在围绝经期和绝经后女性中，MAOA基因c.1460 CT和c.1460 CT + TT基因型（分别为OR = 1.83；校正p值 = 0.009和OR = 1.85；校正p值 = 0.003），以及MTHFR基因c.677 TT和c.677 CT + TT基因型（分别为OR = 3.52；校正p值 = 0.00009和OR = 2.06；校正p值 = 0.0006），还有绝经后女性中COMT基因c.472 GA和COMT基因c.472 GA + AA基因型（分别为OR = 2.23；校正p值 = 0.03和OR = 2.17；校正p值 = 0.027），在抑郁女性患者中的这些变异频率显著高于对照组，而ESR1基因454(-351)AG和454(-351)AG + GG基因型与绝经后女性较低的抑郁风险相关（分别为OR = 0.48；校正p值 = 0.012和OR = 0.52；校正p值 = 0.015）。
我们的研究证实了MAOA和MTHFR基因多态性与更年期抑郁症有关，并提供了证据表明COMT和ESR1基因也可能在绝经后女性抑郁情绪易感性中起作用。
