Genes for enzymes regulating dehydroepiandrosterone sulfonation are associated with levels of dehydroepiandrosterone sulfate in polycystic ovary syndrome

Mark O. Goodarzi, Heath J. Antoine, Ricardo Azziz

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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. Dehydroepiandrosterone (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 aim 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: A total of 287 white women with PCOS and 187 controls participated in the study. Main Measurements: SULT2A1 and STS genotype and DHEAS levels were measured. 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. Conclusion: This study presents genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited AA excess of PCOS.

Original languageEnglish (US)
Pages (from-to)2659-2664
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number7
DOIs
StatePublished - Jan 1 2007

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Sulfonation
Dehydroepiandrosterone Sulfate
Dehydroepiandrosterone
Polycystic Ovary Syndrome
Steryl-Sulfatase
Genes
Polymorphism
Enzymes
Single Nucleotide Polymorphism
Nucleotides
Androgens
Haplotypes
Endocrinology
Los Angeles
Metabolites
Modulators
Alleles
Genotype
Association reactions

ASJC Scopus subject areas

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

Cite this

Genes for enzymes regulating dehydroepiandrosterone sulfonation are associated with levels of dehydroepiandrosterone sulfate in polycystic ovary syndrome. / Goodarzi, Mark O.; Antoine, Heath J.; Azziz, Ricardo.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 7, 01.01.2007, p. 2659-2664.

Research output: Contribution to journalArticle

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abstract = "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. Dehydroepiandrosterone (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 aim 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: A total of 287 white women with PCOS and 187 controls participated in the study. Main Measurements: SULT2A1 and STS genotype and DHEAS levels were measured. 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. Conclusion: This study presents genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited AA excess of PCOS.",
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