Association study of androgen signaling pathway genes in polycystic ovary syndrome

Single-nucleotide polymorphisms in the FKBP4 gene,which codes for a co-chaperone of the androgen receptor, may be associated with polycystic ovary syndrome and body mass index.


Aline Ketefian, M.D., Michelle R. Jones, Ph.D., Ronald M. Krauss, M.D., Yii-Der I. Chen, Ph.D., Richard S. Legro, M.D., Ricardo Azziz, M.D., M.P.H., Mark O. Goodarzi, M.D., Ph.D.

Volume 105, Issue 2, Pages 467-473



To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS).


Two groups of women with PCOS and control women (discovery and replication cohorts), were genotyped for single-nucleotide polymorphisms 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.


Tertiary referral center.


Discovery cohort: 354 women with PCOS and 161 control women. Replication cohort: 397 women with PCOS and 306 control women.


Phenotypic and genotypic assessment.

Main Outcome Measure(s):

Single-nucleotide polymorphism genotypes, association with PCOS status, and androgenic and metabolic parameters.


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.


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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