期刊
FERTILITY AND STERILITY
卷 105, 期 2, 页码 467-+出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2015.09.043
关键词
PCOS; androgen receptor; chaperones; co-chaperones
资金
- National Institutes of Health [R01-HD29364, K24-HD01346, R01-DK79888, U54-HD034449, U19-HL069757]
- National Center for Research Resources [M01-RR00425, U54 RR026071]
- Winnick Clinical Scholars Award
- Helping Hand of Los Angeles, Inc
- National Center for Advancing Translational Sciences, CTSI [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center to the Southern California Diabetes Research Center [P30-DK063491]
Objective: To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS). Design: Two groups of women with PCOS and control women (discovery and replication cohorts), were genotyped for single-nucleotide polymorphisms (SNPs) in eight genes for AR chaperones and co-chaperones: HSPA1A, HSPA8, ST13, STIP1, PTGES3, FKBP4, BAG1, and STUB1. Single-nucleotide polymorphisms were tested for association with PCOS status and with androgenic and metabolic parameters. Setting: Tertiary referral center. Patient(s): Discovery cohort: 354 women with PCOS and 161 control women. Replication cohort: 397 women with PCOS and 306 control women. Intervention(s): Phenotypic and genotypic assessment. Main Outcome Measure(s): Single-nucleotide polymorphism genotypes, association with PCOS status, and androgenic and metabolic parameters. Result(s): In the discovery cohort, FKBP4 SNPs rs2968909 and rs4409904 were associated with lower odds of PCOS. This finding was not confirmed in the replication cohort analysis; however, when combining the two cohorts, rs4409904 was associated with lower odds of PCOS. In subjects with PCOS in the replication cohort as well as in the combined cohort, rs2968909 was associated with lower body mass index. Conclusion(s): Single-nucleotide polymorphisms in FKBP4, which codes for the AR co-chaperone FKBP52, may be associated with PCOS and body mass index in patients with PCOS. The remaining genes studied do not seem to be major contributors to the development of PCOS. These findings warrant confirmation in future studies, and genes encoding other androgen pathway components remain to be studied. (C) 2016 by American Society for Reproductive Medicine.
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