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Variants in estrogen-related genes and risk of Parkinson's disease

Authors


  • Relevant conflicts of interest/financial disclosures: The major aspects of the research program were funded by the National Institutes of Health (7 R01 ES010751-10). Sun Ju Chung has been employed as Assistant Professor, Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea and has received funding for travel from Glaxo-SmithKline Korea. Sebastian M. Armasu has been employed as a Statistician I, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic (Rochester, MN) and has received funding from the National Institutes of Health (7 R01 ES010751-10 [coinvestigator], 1 P50 CA136393-01A1 [coinvestigator], 5 U01 HG004735-02 [coinvestigator]). Joanna M. Biernacka has been employed as Assistant Professor of Biostatistics and Psychiatry, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic (Rochester, MN) and has received funding from the National Institutes of Health (1 P20 AA017830-01 [coinvestigator], 7 R01 ES010751-10 [coinvestigator], 1 R03 AA019570-01 [primary investigator], 1 R01 MH079261-01A2 [coinvestigator]). Timothy G. Lesnick has been employed as a Statistician III, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic (Rochester, MN), may accrue revenue from pending patent applications related to the prediction of Parkinson disease, and receives research support from the National Institutes of Health (7 R01 ES010751-10 [coinvestigator]). David N. Rider has been employed as a Senior Analyst/Programmer, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic (Rochester, MN) and has no disclosures to report. Julie M. Cunningham has been employed as an Assistant Professor of Laboratory Medicine and Pathology, Mayo Genomics Research Center, Mayo Clinic (Rochester, MN) and has no disclosures to report. Demetrius M. Maraganore is the Ruth Cain Ruggles Chairman of the Department of Neurology, and Medical Director of the Neurological Institute, NorthShore University HealthSystem (Evanston, IL). He may accrue revenue from pending patent applications related to the prediction of Parkinson disease and the treatment of neurodegenerative disease, has received license fee payments and royalty payments from Alnylam Pharmaceuticals (method to treat Parkinson's disease), and receives research support from the National Institutes of Health (7 R01 ES010751-10 [primary investigator]).

    Full financial disclosures and author roles can be found in the online version of this article.

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. © 2011 Movement Disorder Society

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