TY - JOUR
T1 - Association study of androgen signaling pathway genes in polycystic ovary syndrome
AU - Ketefian, Aline
AU - Jones, Michelle R.
AU - Krauss, Ronald M.
AU - Chen, Yii Der I.
AU - Legro, Richard S.
AU - Azziz, Ricardo
AU - Goodarzi, Mark O.
N1 - Funding Information:
Supported by National Institutes of Health grants R01-HD29364 and K24-HD01346 (to R.A.), R01-DK79888 (to M.O.G.), U54-HD034449 (to R.S.L.), and U19-HL069757 (to R.M.K.); National Center for Research Resources grant M01-RR00425 (to the Cedars-Sinai General Clinical Research Center), grant U54 RR026071 (to Penn State Clinical and Translational Science Institute [CTSI]); the Winnick Clinical Scholars Award (to M.O.G.); and an endowment from the Helping Hand of Los Angeles, Inc. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences , CTSI grant UL1TR000124 , and National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant P30-DK063491 to the Southern California Diabetes Research Center.
Funding Information:
Supported by National Institutes of Health grants R01-HD29364 and K24-HD01346 (to R.A.), R01-DK79888 (to M.O.G.), U54-HD034449 (to R.S.L.), and U19-HL069757 (to R.M.K.); National Center for Research Resources grant M01-RR00425 (to the Cedars-Sinai General Clinical Research Center), grant U54 RR026071 (to Penn State Clinical and Translational Science Institute [CTSI]); the Winnick Clinical Scholars Award (to M.O.G.); and an endowment from the Helping Hand of Los Angeles, Inc. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant P30-DK063491 to the Southern California Diabetes Research Center.
Publisher Copyright:
© 2016 American Society for Reproductive Medicine
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - PCOS
KW - androgen receptor
KW - chaperones
KW - co-chaperones
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U2 - 10.1016/j.fertnstert.2015.09.043
DO - 10.1016/j.fertnstert.2015.09.043
M3 - Article
C2 - 26493122
AN - SCOPUS:84949266819
SN - 0015-0282
VL - 105
SP - 467-473.e4
JO - Fertility and sterility
JF - Fertility and sterility
IS - 2
ER -