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

Agata Różycka; Radosław Słopień; Agnieszka Słopień; Jolanta Dorszewska; Agnieszka Seremak-Mrozikiewicz; Margarita Lianeri; Małgorzata Maciukiewicz; Alina Warenik-Szymankiewicz; Teresa Grzelak; Grażyna Kurzawińska; Krzysztof Drews; Andrzej Klejewski; Paweł P Jagodziński

doi:10.1016/j.maturitas.2015.10.011

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

Maturitas. 2016 Feb:84:42-54. doi: 10.1016/j.maturitas.2015.10.011. Epub 2015 Oct 30.

Affiliations

¹ Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland. Electronic address: arozycka@ump.edu.pl.
² Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
³ Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, 27/33 Szpitalna St., 60-572 Poznan, Poland.
⁴ Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355 Poznan, Poland.
⁵ Department of Perinatology and Women's Diseases, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland; Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, 71b Wojska Polskiego St., 60-630 Poznan, Poland.
⁶ Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
⁷ Department of Psychiatric Genetics, Poznan University of Medical Sciences, 27/33 Szpitalna St., 60-572 Poznan, Poland.
⁸ Laboratory of Biology of Civilization-Related Diseases, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
⁹ Department of Perinatology and Women's Diseases, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
¹⁰ Department of Nursing, Poznan University of Medical Sciences, 11 Smoluchowskiego St., 60-179 Poznan, Poland.

PMID: 26620113
DOI: 10.1016/j.maturitas.2015.10.011

Abstract

Objective: 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.

Methods: 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.

Results: 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.).

Conclusions: 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.

Keywords: COMT; ESR1; Gene polymorphism; MAOA; MTHFR; Menopausal depression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics
Adult
Aged
Catechol O-Methyltransferase / genetics*
Depression / genetics*
Depressive Disorder / genetics*
Estrogen Receptor alpha / genetics*
Female
Genotype
Humans
Menopause / psychology
Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics
Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
Middle Aged
Minor Histocompatibility Antigens
Monoamine Oxidase / genetics*
Norepinephrine Plasma Membrane Transport Proteins / genetics
Polymorphism, Single Nucleotide
Psychiatric Status Rating Scales
Receptor, Serotonin, 5-HT1B / genetics*
Receptor, Serotonin, 5-HT2A / genetics
Receptor, Serotonin, 5-HT2C / genetics
Receptors, GABA-A / genetics
Risk Factors
Tryptophan Hydroxylase / genetics

Substances

ESR1 protein, human
Estrogen Receptor alpha
GABRB1 protein, human
Minor Histocompatibility Antigens
Norepinephrine Plasma Membrane Transport Proteins
Receptor, Serotonin, 5-HT1B
Receptor, Serotonin, 5-HT2A
Receptor, Serotonin, 5-HT2C
Receptors, GABA-A
SLC6A2 protein, human
TPH1 protein, human
TPH2 protein, human
Tryptophan Hydroxylase
Monoamine Oxidase
monoamine oxidase A, human
MTHFR protein, human
Methylenetetrahydrofolate Reductase (NADPH2)
MTHFD1 protein, human
Methylenetetrahydrofolate Dehydrogenase (NADP)
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
MTR protein, human
COMT protein, human
Catechol O-Methyltransferase