Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
SNP Communications
Genetic Variation and Haplotype Structures of the Glutathione S-transferase Genes GSTA1 and GSTA2 in Japanese Colorectal Cancer Patients
Keiko MAEKAWATetsuya HAMAGUCHIYoshiro SAITONaoko TATEWAKIKouichi KUROSENahoko KANIWATakako EGUCHI NAKAJIMAKen KATOYasuhide YAMADAYasuhiro SHIMADATeruhiko YOSHIDANaoyuki KAMATANITakashi URAMiyuki SAITOKei MURONozomu FUSETakayuki YOSHINOToshihiko DOIAtsushi OTSUNagahiro SAIJOJun-ichi SAWADAHaruhiro OKUDAYasuhiro MATSUMURA
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2011 Volume 26 Issue 6 Pages 646-658

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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.

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© 2011 by The Japanese Society for the Study of Xenobiotics
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