title: The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland. Electronic address: arozycka@ump.edu.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Różycka
authors.affiliation: Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
authors.forename: Radosław
authors.initials: R
authors.lastname: Słopień
authors.affiliation: Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, 27/33 Szpitalna St., 60-572 Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Słopień
authors.affiliation: Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355 Poznan, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Dorszewska
authors.affiliation: 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.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Seremak-Mrozikiewicz
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
authors.forename: Margarita
authors.initials: M
authors.lastname: Lianeri
authors.affiliation: Department of Psychiatric Genetics, Poznan University of Medical Sciences, 27/33 Szpitalna St., 60-572 Poznan, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Maciukiewicz
authors.affiliation: Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Warenik-Szymankiewicz
authors.affiliation: Laboratory of Biology of Civilization-Related Diseases, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Grzelak
authors.affiliation: Department of Perinatology and Women's Diseases, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Kurzawińska
authors.affiliation: Department of Perinatology and Women's Diseases, Poznan University of Medical Sciences, 33 Polna St., 60-535 Poznan, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Drews
authors.affiliation: Department of Nursing, Poznan University of Medical Sciences, 11 Smoluchowskiego St., 60-179 Poznan, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Klejewski
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000328:Adult; D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008593:Menopause / Q000523:psychology; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D008995:Monoamine Oxidase / Q000235:genetics*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics; D012307:Risk Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C546264:GABRB1 protein, human; D015778:Minor Histocompatibility Antigens; D050484:Norepinephrine Plasma Membrane Transport Proteins; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011963:Receptors, GABA-A; C493227:SLC6A2 protein, human; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: COMT; ESR1; Gene polymorphism; MAOA; MTHFR; Menopausal depression