Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk
Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk
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DOI：
10.1089/gtmb.2012.0161
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发表时间：
2013-01-01
影响因子：
1.4
通讯作者：
Freedland, Stephen J.
中科院分区：
文献类型：
--
作者：
Grant, Delores J.;Hoyo, Cathrine;Freedland, Stephen J.
目的：尿苷二磷酸-葡萄糖醛酸转移酶2B（UGT 2B）酶结合睾酮代谢物，使其能够在人体内排泄。UGT 2B遗传变异的功能意义从未在人类中描述过。我们评估了UGT 2B变体与血浆雄甾烷-3 α，17 β-二醇-葡萄糖醛酸苷（AAG）水平和前列腺癌风险的关系。结果：在150名对照者的血清中测定AAG水平，并与UGT 2B 17、UGT 2B 15和UGT 2B 7的多态性进行比较。对来自对照组（301例）和病例组（148例）的基因组DNA进行多态性基因分型，并使用非条件logistic回归分析计算比值比（OR）和95%置信区间（95%CI）。具有两个UGT 2B 17拷贝与白人对照组中较高的AAG水平相关（p = 0.02），但与黑人对照组无关（p = 0.82）。经年龄和种族校正后的Logistic回归模型显示，UGT 2B 15（D85 Y）多态性G等位基因纯合性与前列腺癌风险直接相关（OR = 2.70，95%CI = 1.28，5.55）。结论：虽然小样本量限制了推断，但我们的研究结果表明，UGT 2B 17拷贝数变异（CNV）与白人血清AAG水平之间存在相关性，但出乎意料的是，黑人中没有相关性。这一新的观察结果表明，黑人中AAG水平的遗传决定因素与UGT 2B 17 CNV无关。这项研究重复了显示UGT 215（D85 Y）与前列腺癌风险增加相关的结果。
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-3 alpha, 17 beta-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.