Context: The adrenal androgen (AA) metabolite dehydroepiandrosterone-sulfate (DHEAS) is often elevated in women with polycystic ovary syndrome (PCOS); AA excess in PCOS appears to be, in part, a heritable trait. DHEA sulfonation is controlled by the enzymes DHEA sulfotransferase (SULT2A1) and steroid sulfatase (STS). Polymorphisms in these genes have not been evaluated as modulators of DHEAS level in PCOS.

Objective: The objective of the study was to test the hypothesis that variants in the SULT2A1 and STS genes are associated with DHEAS levels in women with PCOS.

Design: Women with and without PCOS were genotyped for seven single nucleotide polymorphisms (SNPs) in SULT2A1 and seven SNPs in STS. SNPs and haplotypes were determined and tested for association with DHEAS.

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: 287 White women with PCOS and 187 controls.

Main Measurements: SULT2A1 and STS genotype, DHEAS levels.

Results: In women with PCOS, SNP rs182420 in SULT2A1 was associated with DHEAS (P=0.0035). Two haplotypes carrying the minor allele of rs182420 were also associated with DHEAS (P=0.04 each). Variants within STS were not associated with DHEAS level. No associations were observed in control women.

Conclusions: This study presents genetic evidence suggesting a potential role of DHEA sulfotransferase but not steroid sulfatase in the inherited AA excess of PCOS.