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Variants in SULT2A1 affect the DHEA sulphate to DHEA ratio in patients with polycystic ovary syndrome but not the hyperandrogenic phenotype



Variants in SULT2A1 affect the DHEA sulphate to DHEA ratio in patients with polycystic ovary syndrome but not the hyperandrogenic phenotype



Journal of Clinical Endocrinology and Metabolism 98(9): 3848-3855



Context.Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in PCOS and the heritability of DHEAS serum levels, genes encoding the enzymes that control the sulfation of dehydroepiandrosterone (DHEA) to DHEAS and vice versa are obvious candidate genes to explain part of the heritability of PCOS.Objective.To determine the role of genetic variants in sulfotransferase (SULT2A1), 3-phosphoadenosine 5-phosphosulfate synthase isoform 2 (PAPSS2) and steroid sulfatase (STS) in PCOS and in hormone levels related to the hyperandrogenic phenotype of PCOS.Design.Candidate-gene study.Patients.Discovery set consisted of 582 patients and 2017 controls.Main outcome measures.A pruned subset of 28 SNPs in SULT2A1, PAPSS2 and STS was generated based on pairwise genotypic correlation. Association with PCOS was tested and we studied whether the SNPs modulate DHEAS levels, DHEA levels and their ratio in PCOS. Significant SNPs were replicated in an independent sample of patients.Results.None of the SNPs in SULT2A1, PAPSS2 and STS constituted risk alleles for PCOS. SNP rs2910397 in SULT2A1 decreased the DHEAS to DHEA ratio in PCOS by 5% in the discovery sample. Meta-analysis of discovery and replication sample resulted in a combined effect of -0.095 (p-value = 0.027). However, carrying the minor T-allele did not contribute to differences in hyperandrogenic phenotype, including levels of testosterone and androstenedione, of PCOS patients.Conclusions.Genetic variants in SULT2A1, PAPSS2 and STS do not predispose to PCOS. Although a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other androgenic hormone levels were observed.

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Accession: 056848220

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PMID: 23861462

DOI: 10.1210/jc.2013-1976



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