Aline Ketefian1, Michelle R Jones2, Ronald M Krauss3, Yii-Der I Chen4, Richard S Legro5, Ricardo Azziz6, Mark O Goodarzi7. 1. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 2. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. 3. Children's Hospital Oakland Research Institute, Oakland, California. 4. Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California. 5. Department of Obstetrics and Gynecology, Pennsylvania State College of Medicine, Hershey, Pennsylvania. 6. Departments of Obstetrics and Gynecology and Medicine, Georgia Regents University, Augusta, Georgia. 7. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: mark.goodarzi@cshs.org.
Abstract
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.
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.
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