Genetic and phenotypic variation in UGT2B17, a testosterone-metabolizing enzyme, is associated with BMI in males

Pharmacogenetics and Genomics
Andy Z X ZhuRachel F Tyndale

Abstract

A number of candidate gene and genome-wide association studies have identified significant associations between single nucleotide polymorphisms, particularly in FTO and MC4R, and body weight. However, the association between copy number variation and body weight is less understood. Anabolic androgenic steroids, such as testosterone, can regulate body weight. In humans, UDP-glucuronosyltransferase 2B17 (UGT2B17) metabolizes testosterone to a metabolite, which is readily excreted in urine. We investigate the association between genetic and phenotypic variation in UGT2B17 and body weight. UGT2B17 deletion was genotyped and in-vivo UGT2B17 enzymatic activity (as measured by the 3-hydroxycotinine glucuronide to free 3-hydroxycotinine ratio) was measured in 400 Alaska Native individuals and 540 African Americans. In Alaska Native people, UGT2B17 deletion was strongly associated with lower BMI in male individuals (P<0.001), but not in female individuals, consistent with testosterone being a male dominant steroid. The sex-specific association between UGT2B17 deletion and lower BMI was also observed in African Americans (P=0.01 in male individuals). In both populations, UGT2B17 deletion was significantly associated with lower measured i...Continue Reading

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Sep 17, 2015·Reviews in Endocrine & Metabolic Disorders·Eberhard Nieschlag, Elena Vorona
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Jan 5, 2020·Clinical Pharmacology and Therapeutics·Haeyoung ZhangBhagwat Prasad
Mar 15, 2020·The Journal of Clinical Endocrinology and Metabolism·Ying-Ju LinFuu-Jen Tsai

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Methods Mentioned

BETA
PCR

Software Mentioned

STATA
CopyCaller
R
Bioconductor

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