RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 1048
OP 1054
VO 32
IS 9
A1 Mayumi Saeki
A1 Yoshiro Saito
A1 Hideto Jinno
A1 Toshiko Tanaka-Kagawa
A1 Akiko Ohno
A1 Shogo Ozawa
A1 Kazuyuki Ueno
A1 Shiro Kamakura
A1 Naoyuki Kamatani
A1 Kazuo Komamura
A1 Masafumi Kitakaze
A1 Jun-ichi Sawada
YR 2004
UL http://dmd.aspetjournals.org/content/32/9/1048.abstract
AB 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