Independent confirmation of association between metabolic phenotypes of polycystic ovary syndrome and variation in the type 6 17beta-hydroxysteroid dehydrogenase gene

J Clin Endocrinol Metab. 2009 Dec;94(12):5034-8. doi: 10.1210/jc.2009-0931. Epub 2009 Oct 16.

Abstract

Context: Few candidate genes for polycystic ovary syndrome (PCOS) are widely agreed upon largely due to lack of replication. Type 6 17beta-hydroxysteroid dehydrogenase (HSD17B6) gene expression is increased in PCOS ovarian theca. Previous genetic study of HSD17B6 reported significant association of rs898611 with PCOS risk and metabolic phenotypes.

Objective: Our objective was to replicate association between polymorphisms in HSD17B6 and PCOS in a well-characterized replication cohort.

Design: We conducted a case-control association study.

Setting: Subjects were recruited from reproductive endocrinology clinics; controls were recruited from the surrounding communities of the University of Alabama at Birmingham and Cedars-Sinai Medical Center in Los Angeles. Genotyping occurred at Cedars-Sinai Medical Center.

Participants: Participants included 335 White women with PCOS and 198 White controls.

Main measurements: We assessed HSD17B6 genotype, PCOS status, and metabolic traits.

Results: The minor allele of rs898611 was not associated with PCOS; however, it was associated with increased body mass index (P = 0.031), increased fasting insulin (P = 0.008), decreased fasting glucose/insulin ratio (P = 0.038), and increased homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.021). rs10459247 and rs10876920 were associated with increased fasting insulin (P = 0.031 and 0.019, respectively), and rs10876920 was also associated with increased HOMA-IR (P = 0.046). Haplotype T-A-T-C was associated with reduced fasting insulin (P = 0.046), and haplotype C-A-C-T was associated with increased body mass index (P = 0.032).

Conclusions: Although we did not replicate association between PCOS and rs898611, we replicated associations of this variant and others in HSD17B6 with metabolic traits. These replication data suggest a role for HSD17B6 in PCOS. How HSD17B6, an enzyme involved in steroid metabolism, may influence BMI and insulin resistance in PCOS remains to be determined.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Body Mass Index
  • Cohort Studies
  • Female
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Humans
  • Insulin / blood
  • Phenotype
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / metabolism*
  • Polymorphism, Single Nucleotide
  • Racemases and Epimerases / genetics*
  • Risk
  • Steroids / metabolism
  • White People

Substances

  • Insulin
  • Steroids
  • HSD17B6 protein, human
  • Racemases and Epimerases