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

Michelle R. Jones, Ruchi Mathur, Jinrui Cui, Xiuqing Guo, Ricardo Azziz, Mark O. Goodarzi

Research output: Contribution to journalArticle

21 Scopus citations


Context:Fewcandidate genes for polycystic ovary syndrome (PCOS) are widely agreeduponlargely due to lack of replication. Type 6 17β-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.

Original languageEnglish (US)
Pages (from-to)5034-5038
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
StatePublished - Dec 2009


ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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