Association of SULT2A1 allelic variants with plasma adrenal androgens and prostate cancer in African American men

The Journal of Steroid Biochemistry and Molecular Biology
Teresa W WilbornCharles N Falany

Abstract

Dehydroepiandrosterone (DHEA) sulfate which is present at micromolar levels in the plasma, can be desulfated to supply free DHEA for metabolism to androgens or estrogens in peripheral tissues. Human cytosolic sulfotransferase (SULT) 2A1 catalyzes DHEA sulfation in the adrenal cortex. Three SULT2A1 nonsynonymous coding single nucleotide polymorphisms (SNPs), identified only in African Americans (AA), are associated with decreased levels of activity and expression as compared to wild-type cDNA when expressed in COS cells. To test whether the SNPs are associated with decreased plasma androgens, 124 normal AA men were genotyped and plasma DHEA, DHEA-sulfate and testosterone levels determined. The two SNPs identified in these participants occurred at allelic frequencies of 0.044 (G187C) and 0.101 (G781A). The G187C SNP was highly linked to the G781A SNP. Although no differences in hormone levels were associated with the individual SNPs, a significant increase in the DHEA:DHEA-sulfate ratio was observed in participants with a heterozygous G187C/G781A genotype. Increased free DHEA levels may result in increased testosterone synthesis and stimulation in the prostate, therefore a group of AA prostate cancer (PC) patients and controls we...Continue Reading

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Citations

Dec 23, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Camille C RaginEmanuela Taioli
Jan 30, 2013·Drug Metabolism and Pharmacokinetics·Su-Jun LeeJae-Gook Shin
Feb 24, 2009·The Journal of Urology·Nina Mononen, Johanna Schleutker
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Jun 11, 2021·Expert Opinion on Drug Metabolism & Toxicology·Katsuhisa KurogiMing-Cheh Liu
Aug 20, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elahe A MostaghelR Bruce Montgomery

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