Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15

Wilson, Willie; Villena, Fernando Pardo-Manuel de; Lyn‐Cook, Beverly; Chatterjee, Pranam; Bell, Timothy A.; Detwiler, David A.; Gilmore, Rodney C.; Valladeras, Isis C.; Wright, Camille C.; Threadgill, David W.; Grant, Delores J.

doi:10.1016/j.ygeno.2004.06.011

Cited by 136 publications

(126 citation statements)

References 27 publications

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“…Previous studies have demonstrated deletion of the UGT2B17 gene. 13,14 We have demonstrated recently an association between the UGT2B17 deletion and urinary testosterone excretion. 15 Homozygous carriers of the deletion (del/del) allele have very low or undetectable levels of testosterone in the urine.…”

Section: Introductionmentioning

confidence: 92%

“…13 The deletion-specific primers (J-markers) and the exon 6-specific primers (Table 3) were used in a standard PCR protocol (AmpliTaq DNA Polymerase, Applied Biosystems, Foster City, CA, USA) and the products were identified in a 2% agarose gel. Owing to low DNA concentrations, some of the samples were analyzed with SYBR green Master Mix (Applied Biosystems), and the product formations was followed on an ABI Prism7700 (Applied Biosystems).…”

Section: Genotyping Of the Ugt2b17 Deletionmentioning

confidence: 99%

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Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate

et al. 2007

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Metabolism of androgens includes glucuronidation, the major pathway of steroid elimination in several steroid target tissues. Glucuronidation is catalysed by UDP-glucuronosyltransferases (UGTs). UGT2B17 has been shown to be particularly active against androgens and is highly abundant in the prostate. Recently, we discovered that deletion of the UGT2B17 gene is associated with low or undetectable urinary testosterone levels. Here, we determined the phenotypic outcome of the deletion by quantifying the UGT2B17 mRNA expression in normal prostate tissues in individuals with different genotypes. Additionally, the frequency of UGT2B17 deletion polymorphism was studied in a Swedish population-based case-control study including 176 patients diagnosed with prostate cancer and 161 controls. We found that the individuals homozygous for the insertion allele expressed 30 times more UGT2B17 mRNA in prostate tissue than the heterozygotes. Carriers of the deletion allele had a significantly increased risk of prostate cancer (OR ¼ 2.07; 95% CI ¼ 1.32-3.25). In conclusion, these results show the UGT2B17 deletion polymorphism is associated with prostate cancer risk.

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Section: Introductionmentioning

confidence: 92%

Section: Genotyping Of the Ugt2b17 Deletionmentioning

confidence: 99%

Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate

et al. 2007

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“…Samples that were analyzed for the UGT2B17 CNV were quantified with PicoGreen as described above and genotyped using the ABI 7900HT (Applied Biosystems) platform and commercially available TaqMan CNV assays. Each sample was assayed in quadruplicate and compared with controls previously genotyped (Wilson et al, 2004). Data analysis was accomplished using SDS v2.4 and CopyCaller v1.0 (Applied Biosystems), and the confidence level was ‡ 0.99.…”

Section: D85ymentioning

confidence: 99%

“…UGT2B17 has a copy number variant (CNV) that is present in 0, 1, or 2 copies (Wilson et al, 2004;Jakobsson et al, 2006), while an UGT2B15 variant, UGT2B15 D85Y , has a missense polymorphism at codon 85 that changes an aspartic acid residue (D allele) to a tyrosine residue (Y allele), resulting in an increased V max . The resulting phenotype of the enzyme leads to quicker androgen metabolite clearance, while the wild type confers lower clearance, possibly raising the effective amount of steroids within the prostate (Levesque et al, 1997;Chouinard et al, 2008).…”

mentioning

confidence: 99%

Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk

Grant

Hoyo

Oliver

et al. 2013

Genetic Testing and Molecular Biomarkers

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Aims: Uridine diphosphate-glucuronosyltransferase 2B (UGT2B) enzymes conjugate testosterone metabolites to enable their excretion in humans. The functional significance of the UGT2B genetic variants has never been described in humans. We evaluated UGT2B variants in relation to plasma androstane-3a,17b-diol-glucuronide (AAG) levels and the prostate cancer risk. Results: AAG levels were measured in sera from 150 controls and compared to the polymorphisms of UGT2B17, UGT2B15, and UGT2B7. Genomic DNA from controls (301) and cases (148) was genotyped for the polymorphisms, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analyses. Having two copies of UGT2B17 was associated with higher AAG levels in controls among Whites ( p = 0.02), but not Blacks ( p = 0.82). Logistic regression models adjusting for age and race revealed that homozygosity for the G allele of the UGT2B15 D85Y polymorphism was directly associated with the prostate cancer risk (OR = 2.70, 95% CI = 1.28, 5.55). Conclusions: While the small sample size limits inference, our findings suggest that an association between the UGT2B17 copy number variant (CNV) and serum AAG levels in Whites, but unexpectedly not in Blacks. This novel observation suggests that genetic determinants of AAG levels in Blacks are unrelated to the UGT2B17 CNV. This study replicates the results that show an association of UGT215 D85Y with an increased prostate cancer risk.

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“…In contrast to the UGT1A first exons, it appears that fewer mutations affecting the coding regions occurred in these genes, which indicates a more conservative structure for UGT2B genes [48][49][50]. Polymorphic deletions were shown to occur for UGT2B genes namely UGT2B17 and UGT2B28 (Jakobsson et al, 2006;McCarroll et al, 2006;Wilson et al, 2004). In fact, copy-number variations of these two genes have been described with divergent frequencies among ethnic populations and surely contribute as a source of phenotypic differences (Spielman et al, 2007).…”

Section: The Human Ugt2 Family Membersmentioning

confidence: 99%

UGT genomic diversity: beyond gene duplication

Guillemette

Lévesque

Harvey

et al. 2009

Drug Metabolism Reviews

121

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Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15

Cited by 136 publications

References 27 publications

Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate

Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate

Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk

UGT genomic diversity: beyond gene duplication

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