Nonreplication of the type 5 17β-hydroxysteroid dehydrogenase gene association with polycystic ovary syndrome

Context: Increased androgen production is a primary feature of polycystic ovary syndrome (PCOS) and appears to be an inherited trait. The gene for the steroidogenic enzyme type 5 17β hydroxysteroid dehydrogenase (HSD17B5) was implicated as a candidate for the hyperandrogenemia of PCOS by a previous study that demonstrated an association of a single nucleotide polymorphism (SNP) in the promoter of this gene with PCOS. Objective: The objective of the study was to replicate the previous report of association between the HSD17B5 gene and PCOS risk by genotyping the promoter SNP (as well as other SNPs in the region to provide improved coverage of the gene) in a large, well-characterized cohort suitable for replication study. Design: Women with and without PCOS were genotyped for five SNPs in HSD17B5. SNPs and haplotypes were determined and tested for association with PCOS risk and phenotypic markers of PCOS. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: Participants included 287 white women with PCOS and 187 white controls. Main Measurements: HSD17B5 genotype, PCOS risk, and testosterone levels were measured. Results: No SNP or haplotype was significantly associated with PCOS risk, testosterone, or any of the traits tested. Conclusions: These data suggest that polymorphisms in the HSD17B5 gene are not associated with PCOS risk or elevated testosterone as previously reported.