Catalog of 320 single nucleotide polymorphisms (SNPs) in 20 quinone oxidoreductase and sulfotransferase genes

Abstract

Single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes, transporters, receptors, and other drug targets have been widely implicated as contributors to differences among individuals as regards the efficacy and toxicity of many medications, as well as the susceptibility to complex diseases. By combining the polymerase chain reaction (PCR) technique with direct sequencing, we screened genomic DNAs from 48 Japanese volunteers for SNPs in genes encoding three quinone oxidoreductases (NQO1, NQO2, and PIG3) and 17 sulfotransferases (SULT1A1, SULT1A2, SULT1A3, SULT1C1, SULT1C2, SULT2A1, SULT2B1, ST1B2, TPST1, TPST2, SULTX3, STE, CST, CHST2, CHST4, and CHST5). In all, we identified 320 SNPs from these 20 loci: 22 within coding elements, 21 in 5Ј flanking regions, 10 in 5Ј untranslated regions, 223 in introns, 19 in 3Ј untranslated regions, and 25 in 3Ј flanking regions. The ratio of transitions to transversions was approximately 2.3 to 1. Of the 22 coding SNPs, 6 were nonsynonymous substitutions that resulted in amino-acid substitutions. The highdensity SNP maps we constructed from this data for each of the quinone oxidoreductases and sulfotransferases examined here should provide useful information for investigations designed to detect association(s) between genetic variations and common diseases or responsiveness to drug therapy.

Inference from the relationships between linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related genes in four Asian populations

“…In fact, this may most possibly result from the ascertainment bias during SNP discovery. Since the investigated sites were previously discovered by using only 48 individuals of Japanese descent (Iida et al 2001a(Iida et al ,b,c, 2002aSaito et al 2001aSaito et al ,b, 2002aSaito et al ,b,c,d, 2003; Unpublished data of Laboratory for Genotyping, SRC) and then scored in 752 Japanese individuals (Kamatani et al 2004; Unpublished data of Laboratory for Genotyping, SRC), more often than not, they tend to have higher population frequencies (Clark et al 2003). Furthermore, since they were genotyped but not resequenced in the other three Malaysian populations, there is a tendency to introduce a bias toward lower frequencies in other populations (Weiss and Clark 2002).…”

Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients

“…SNPs were genotyped by direct sequencing of PCR products from warfarin-treated patients using a capillary sequencer (ABI3730, Applied Biosystems, Foster City, CA), as previously described (Iida et al 2001), and/or the TaqMan assay (Morris et al 1996). The probe sets for the TaqMan assay were obtained from Applied Biosystems.…”

PCTAIRE3: a putative mediator of growth arrest and death induced by CTS-1, a dominant-positive p53-derived synthetic tumor suppressor, in human malignant glioma cells

“…PCTAIRE3 has not been identified as a p53-inducible gene previously. 14 PIG3 encodes a quinone oxireductase 24 possibly involved in an oxidative stress-mediated cell death pathway. 19 To assess whether PCTAIRE3 or PIG3 may mediate p53-or CTS-1-induced cell death, we generated adenoviruses encoding these genes.…”