SNP discovery, expression and cis-regulatory variation in the UGT2B genes.

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.