Genetic Polymorphisms of UGT1A6 in a Japanese Population

Summary: Thirteen single nucleotide polymorphisms (SNPs), including 6 novel ones, were found in exon I and its flanking region of UDP-glucuronosyltransferase (UGT) 1A6 from 195 Japanese subjects. Several novel SNPs were identified, including 269G > A (R90H), 279A>G (S93S), and 308C>A (S103X) in exon 1, and IVS1 + 109C > T, IVS1 + 120A > G, and IVS1 + 142C > T in the intron downstream of exon 1. Among these SNPs, 308C>A confers termination of translation at codon 103, resulting in the production of an immature protein that probably lacks enzymatic activity. The allele frequencies were 0.003 for all the 6 SNPs. In addition, the 3 known nonsynonymous SNPs were detected: 19T>G (S7A), 541A>G (T181A), and 552A>C (R184S) with frequencies of 0.226, 0.218, and 0.226, respectively. High linkage disequilibrium was observed among 19T>G (S7A), 315A>G (L105L), 541A>G (T181A), 552A>C (R184S), and IVS1 + 130G>T, as reported in Caucasian and African-American populations. Then, 11 haplotypes in UGT1A6 were estimated. The novel nonsynonymous variant, 269A or 308A, was shown to be located on the same DNA strand together with 19G, 315G, 541G, 552C, and IVS1 + 130T. Our results provide fundamental and useful information for genotyping UGT1A6 in the Japanese, and probably Asian populations.