Homozygous deletion of the UGT2B17 gene is not associated with osteoporosis risk in elderly Caucasian women

Chew, Shelby; Mullin, Benjamin H.; Lewis, Joshua R.; Spector, Tim D.; Prince, Richard; Wilson, Scott G.

doi:10.1007/s00198-010-1405-0

Cited by 18 publications

(21 citation statements)

References 30 publications

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“…Similarly to the results reported in this previous study, null carriers who never used HRT in our study displayed a higher bone mass than women with one or two alleles. In contrast, Chew et al [29] did not observe any association with the deletion among 1,103 women aged between 70 and 85 years. However, these authors did not document past or current use of HRT in their population sample.…”

Section: Discussionmentioning

confidence: 87%

UGT2B17 gene deletion associated with an increase in bone mineral density similar to the effect of hormone replacement in postmenopausal women

et al. 2011

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Section: Discussionmentioning

confidence: 87%

UGT2B17 gene deletion associated with an increase in bone mineral density similar to the effect of hormone replacement in postmenopausal women

et al. 2011

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“…A study in Chinese individuals suggested an association of a common CNV with osteoporotic fractures17; however, the same variant was not replicated in a follow-up study of individuals of European origin,18 potentially showing population specific effects. Most of the common CNVs are well tagged by common SNPs,19 and thus are easy to identify with a SNP based GWAS.…”

Section: Introductionmentioning

confidence: 97%

A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

et al. 2013

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“…Other testosterone‐related outcomes, such as lower body mass index and increased bone mineral density, are associated with UGT2B17 deletion. However, other studies report conflicting results, possibly due to the high interindividual variability in UGT2B17‐mediated testosterone metabolism. In addition, UGT2B17 genotype is a well‐known confounder in antidoping tests for athletes, where the urinary testosterone to epitestosterone (T/E) ratio is measured after deconjugation with β‐glucuronidase …”

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confidence: 99%

Normalized Testosterone Glucuronide as a Potential Urinary Biomarker for Highly Variable UGT2B17 in Children 7–18 Years

Zhang

Basit

Wolford

et al. 2020

Clin Pharma and Therapeutics

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UDP-glucuronosyltransferase 2B17 (UGT2B17) is a highly variable androgen-metabolizing and drug-metabolizing enzyme. UGT2B17 exhibits a unique ontogeny profile characterized by a dramatic increase in hepatic protein expression from prepubertal age to adulthood. Age, sex, copy number variation (CNV), and single nucleotide polymorphisms only explain 26% of variability in protein expression, highlighting the need for a phenotypic biomarker for predicting interindividual variability in glucuronidation of UGT2B17 substrates. Here, we propose testosterone glucuronide (TG) normalized by androsterone glucuronide (TG/AG) as a urinary UGT2B17 biomarker, and examine the associations among urinary TG/AG and age, sex, and CNV. We performed targeted metabolomics of 12 androgen conjugates with liquid-chromatography tandem mass spectrometry in 63 pediatric subjects ages 7-18 years followed over 7 visits in 3 years. Consistent with the reported developmental trajectory of UGT2B17 protein expression, urinary TG/AG is significantly associated with age, sex, and CNV. In conclusion, TG/AG shows promise as a phenotypic urinary UGT2B17 biomarker.UDP-glucuronosyltransferase 2B17 (UGT2B17) is a highly variable androgen-metabolizing and drug-metabolizing enzyme, showing over a 3,000-fold variability in hepatic protein expression. 1 It is one of the most commonly deleted genes in the human genome with the frequency of the gene deletion event ranging from 16% in Caucasians subjects up to 96% in Asian subjects. 2 However, even among expressers carrying two copies of the UGT2B17 gene, > 160-fold variability in expression has been reported, 3 suggesting that copy number variation (CNV) is not the only determinant of the variability. Indeed, factors such as age, sex, and single nucleotide polymorphisms also affect UGT2B17 expression and activity. Still, only 26% of the variability can be explained by all these factors combined. 4 UGT2B17 also exhibits a unique developmental trajectory. UGT2B17 is minimally expressed in children under 9 years of age (0.11 ± 0.02 pmol/mg protein) but increases ~ 10-fold throughout adolescence to adulthood (1.31 ± 0.15 pmol/mg protein) in its hepatic protein expression. The increase is much more prominent in males compared to females, and adult males have, on average, 2.6-fold higher levels compared to females (1.75 ± 0.20 vs. 0.65 ± 0.18 pmol/mg protein, respectively). 4 Major endogenous substrates for UGT2B17 are C19 androgen steroids, such as

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Homozygous deletion of the UGT2B17 gene is not associated with osteoporosis risk in elderly Caucasian women

Abstract: These data suggest that quantitative real-time PCR is a rapid and efficient technique for determination of candidate CNVs, including the UGT2B17 CNV; however, we found no evidence of an effect of UGT2B17 CNV on osteoporosis risk in elderly Caucasian women.

Cited by 18 publications

References 30 publications

UGT2B17 gene deletion associated with an increase in bone mineral density similar to the effect of hormone replacement in postmenopausal women

UGT2B17 gene deletion associated with an increase in bone mineral density similar to the effect of hormone replacement in postmenopausal women

A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

Normalized Testosterone Glucuronide as a Potential Urinary Biomarker for Highly Variable UGT2B17 in Children 7–18 Years

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