title: Variants in estrogen-related genes and risk of Parkinson's disease.
abstract: Incidence rates of Parkinson's disease are higher in men than in women at all ages, and these differences may be a result of the neuroprotective effects of estrogen on the nigrostriatal pathway. We investigated the association of common variants in 4 estrogen-related genes with Parkinson's disease. Tagging single-nucleotide polymorphisms in the CYP19A1, ESR1, ESR2, and PRDM2 genes were selected from the International Haplotype Map and genotyped in 1103 Parkinson's disease cases from the upper Midwest of the United States and in 1103 individually matched controls (654 unaffected siblings, and 449 unrelated controls from the same region). Of 137 informative single-nucleotide polymorphisms, 2 PRDM2 single-nucleotide polymorphisms were significantly associated with an increased risk of Parkinson's disease at the Bonferroni-corrected significance level of 0.0004 (rs2744690: OR, 1.54; SE(logOR), .109; 99.96% CI, 1.05-2.26; uncorrected P = .0001; rs2744687: OR, 1.53; SE(logOR), .113; 99.96% CI, 1.03-2.29, uncorrected P = .0002); the association was significant in the women-only stratum but not in the men-only stratum. An additional 6 single-nucleotide polymorphisms in PRDM2, 2 in ESR1, 1 in ESR2, and 1 in CYP19A1 had significant P values in the overall sample before Bonferroni correction. None of the single-nucleotide polymorphisms were significantly associated with age at onset of Parkinson's disease after Bonferroni correction. Our results confirm the association of PRDM2 variants with Parkinson's disease susceptibility, especially in women.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Chung
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Armasu
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.forename: David N
authors.initials: DN
authors.lastname: Rider
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Demetrius M
authors.initials: DM
authors.lastname: Maraganore
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009687:Nuclear Proteins; D014157:Transcription Factors; D001141:Aromatase; C561410:CYP19A1 protein, human; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human