Association study of androgen signaling pathway genes in polycystic ovary syndrome

Fertil Steril. 2016 Feb;105(2):467-73.e4. doi: 10.1016/j.fertnstert.2015.09.043. Epub 2015 Oct 20.

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.

Keywords: PCOS; androgen receptor; chaperones; co-chaperones.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Androgens / metabolism*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polycystic Ovary Syndrome / diagnosis
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / metabolism
  • Polymorphism, Single Nucleotide*
  • Protective Factors
  • Risk Factors
  • Signal Transduction / genetics*
  • Tacrolimus Binding Proteins / genetics*
  • Tertiary Care Centers
  • Young Adult

Substances

  • Androgens
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 4