TY - JOUR T1 - SINGLE NUCLEOTIDE POLYMORPHISMS AND HAPLOTYPE FREQUENCIES OF <em>UGT2B4</em> AND <em>UGT2B7</em> IN A JAPANESE POPULATION JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1048 LP - 1054 VL - 32 IS - 9 AU - Mayumi Saeki AU - Yoshiro Saito AU - Hideto Jinno AU - Toshiko Tanaka-Kagawa AU - Akiko Ohno AU - Shogo Ozawa AU - Kazuyuki Ueno AU - Shiro Kamakura AU - Naoyuki Kamatani AU - Kazuo Komamura AU - Masafumi Kitakaze AU - Jun-ichi Sawada Y1 - 2004/09/01 UR - http://dmd.aspetjournals.org/content/32/9/1048.abstract N2 - Both UDP-glucuronosyltransferase 2B4 (UGT2B4) and UGT2B7 are expressed mainly in the human liver and have several overlapping substrates; e.g., catechol estrogens, bile acids, codeine, and carvedilol. To identify novel single nucleotide polymorphisms (SNPs) and haplotypes in a Japanese population, the enhancer/promoter regions, all the exons, and the surrounding intronic regions of UGT2B4 and UGT2B7 were sequenced from 136 Japanese individuals. We found 16 and 21 polymorphisms, including 10 and 4 novel ones in UGT2B4 and UGT2B7, respectively. The novel nonsynonymous SNPs were 1364A&gt;G (K455R) and 1531T&gt;C (C511R) in UGT2B4 and 1192G&gt; A (D398N) in UGT2B7. From linkage disequilibrium analysis, several SNPs in UGT2B7 were found to be highly linked with each other. No close linkage between the SNPs in UGT2B4 and UGT2B7 was observed, indicating that each gene is located within an independent haplotype block. Thus, haplotype analysis was separately performed for the two genes. In UGT2B4, we unambiguously determined 8 haplotypes and inferred an additional 12 haplotypes using an expectation-maximization-based program. In UGT2B7, five haplotypes were unambiguously assigned and an additional eight haplotypes were inferred. The haplotype structure of UGT2B7 was more diverse than that of UGT2B4 in terms of the number of frequent SNPs. In addition, ethnic differences in the UGT2B4*2 and UGT2B7*2 haplotypes between the Japanese and the Caucasian and/or African populations were found. Our findings provide fundamental and useful information for genotyping UGT2B4 and UGT2B7 in the Japanese, and probably other populations. The American Society for Pharmacology and Experimental Therapeutics ER -