Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Pharmacogenomics J. 2012 Aug;12(4):287-96. doi: 10.1038/tpj.2011.2. Epub 2011 Mar 1.
UGT2B enzymes metabolize multiple endogenous and exogenous molecules, including steroid hormones and clinical drugs. However, little is known about the inter-individual variation in gene expression and its determinants. We re-sequenced candidate regulatory regions and the partial coding regions (41.1 kb) of UGT2B genes and identified 332 genetic variants. We measured gene expression in normal breast and liver samples and observed different patterns. The expression levels varied greatly across individuals in both tissues and were significantly correlated with each other in liver. Genotyping of tagging single-nucleotide polymorphisms (SNPs) in the same samples and association tests between genotype and transcript levels identified 62 variants that were associated with at least one UGT2B mRNA levels in either tissue. Most of these cis-regulatory SNPs were not shared between tissues, suggesting that this gene family is regulated in a tissue-specific manner. Our results provide insight into studying the role of UGT2B variation in hormone-dependent cancers and drug response.
UGT2B 酶代谢多种内源性和外源性分子，包括甾体激素和临床药物。然而，个体间基因表达的变化及其决定因素知之甚少。我们重新测序了候选调控区和 UGT2B 基因的部分编码区（41.1kb），并鉴定了 332 个遗传变异。我们测量了正常乳腺和肝脏样本中的基因表达，观察到不同的模式。在这两种组织中，个体间的表达水平差异很大，并且在肝脏中彼此显著相关。对同一样本中的标记单核苷酸多态性（SNP）进行基因分型，并在组织之间进行基因型和转录本水平之间的关联测试，鉴定出 62 个变体，这些变体与至少一种 UGT2B mRNA 水平在任一种组织中相关。这些顺式调控 SNP 大多数在组织之间不共享，这表明该基因家族以组织特异性方式受到调控。我们的研究结果为研究 UGT2B 变异在激素依赖性癌症和药物反应中的作用提供了新的见解。
