The Journal of clinical endocrinology and metabolism

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

PMID 19837928


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. Our objective was to replicate association between polymorphisms in HSD17B6 and PCOS in a well-characterized replication cohort. We conducted a case-control association study. 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 included 335 White women with PCOS and 198 White controls. We assessed HSD17B6 genotype, PCOS status, and metabolic traits. 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). 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.