title: Genetic variation and haplotype structures of the glutathione S-transferase genes GSTA1 and GSTA2 in Japanese colorectal cancer patients.
abstract: Glutathione S-transferases (GSTs) play a vital role in the phase II biotransformation of many chemicals, including anticancer drugs. In this study, to elucidate the haplotype structures of the two closely related alpha-class genes GSTA1 and GSTA2, we screened for genetic variation in 214 Japanese colorectal cancer patients who received oxaliplatin-based chemotherapy. By direct resequencing of the 5'-flanking region, all the exons, and their flanking introns for 107 patients, 29 and 27 variants were identified in GSTA1 and GSTA2, respectively. The known functional single nucleotide polymorphisms (SNPs) -567T>G, -69C>T, and -52G>A in GSTA1*B were found at allele frequencies of 0.140. Of the four major GSTA2 allelic variants reported previously (GSTA2*A, *B, *C, and *E), only GSTA2*B (frequency = 0.154), *C (0.706), and *E (0.140) were detected. Following linkage disequilibrium analysis, haplotypes of both genes were separately estimated. Then, rapid genotyping methods for 7 and 6 SNPs tagging common haplotypes of GSTA1 and GSTA2, respectively, were developed using the single-base extension assay, and an additional 107 patients were genotyped. Finally, haplotype combinations of both genes were classified into 3 major types: GSTA1*A-GSTA2*C, GSTA1*A-GSTA2*B, and GSTA1*B-GSTA2*E. These findings will be useful in pharmacogenomic studies on xenobiotics including anticancer drugs.
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan. maekawa@nihs.go.jp
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Naoko
authors.initials: N
authors.lastname: Tatewaki
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kurose
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Takako
authors.initials: T
authors.lastname: Eguchi Nakajima
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saito
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsu
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sawada
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D044466:Asian People; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D060005:Genotyping Techniques / Q000379:methods; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007438:Introns; D007527:Isoenzymes / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D015262:Xenobiotics / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D015262:Xenobiotics; C484555:GSTA1 protein, human; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha