期刊
FERTILITY AND STERILITY
卷 95, 期 5, 页码 1736-U272出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2011.01.015
关键词
PCOS; INSR; replication; SNP
资金
- Genovum
- Merck Serono
- Organon
- Shering Plough
- MSD
- Serono
- National Institute of Health (NCRR) [R01-HD29364, K24-HD01346, R01-DK79888, M01-RR00425]
- Winnick Clinical Scholars Award
- Helping Hand of Los Angeles, Inc.
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands, Netherlands Organization for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science, Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]
- Research Institute for Diseases in the Elderly [014-93-015, RIDE2]
- Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) [050-060-810]
Objective: To evaluate association with polycystic ovary syndrome (PCOS) of 295 variants in 39 genes central to metabolic insulin signaling and glycogen synthase kinase 3 beta (GSK-3 beta) regulation, followed by replication efforts. Design: Case-control association study, with discovery and replication cohorts. Setting: Subjects were recruited from reproductive endocrinology clinics, and controls were recruited from communities surrounding the University of Alabama at Birmingham and Erasmus Medical Center, Rotterdam. Patient(s): A total of 273 cases with PCOS and 173 control subjects in the discovery cohort; and 526 cases and 3,585 control subjects in the replication cohort. All subjects were caucasian. Intervention(s): Phenotypic and genotypic assessment. Main Outcome Measure(s): Detection of 295 single-nucleotide polymorphisms (SNPs), PCOS status. Result(s): Several SNPs were associated with PCOS in the discovery cohort. Four insulin receptor (INSR) SNPs and three insulin receptor substrate 2 (IRS2) SNPs associated with PCOS were genotyped in the replication cohort. One INSR SNP (rs2252673) replicated association with PCOS. The minor allele conferred increased odds of PCOS in both cohorts, independent of body mass index. Conclusion(s): A pathway-based tagging SNP approach allowed us to identify novel INSR SNPs associated with PCOS, one of which confirmed association in a large replication cohort. (Fertil Steril (R) 2011;95:1736-41. (C)2011 by American Society for Reproductive Medicine.)
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