Identification of 187 single nucleotide polymorphisms (SNPs) among 41 candidate genes for ischemic heart disease in the Japanese population

To investigate whether common variants in the human genetic background are associated with pathogenesis of ischemic heart diseases, we systematically surveyed 41 possible candidate genes for single-nucleotide polymorphisms (S NPs) by directly sequencing 96 independent alleles at each locus, derived f rom 48 unrelated Japanese patients with myocardial infarction, including 25 .8 kb 5' flanking regions, 56.8 kb exonic and 35.4 kb intronic sequences, a nd 1.8 kb 3' flanking regions. In this genomic DNA of nearly 120 kb, we ide ntified 187 SNPs: 55 in 5' flanking regions, seven in 5' untranslated regio ns (UTRs), 52 in coding elements, 64 in introns, eight in 3' UTRs, and one in a 3' flanking region. Among the 52 coding SNPs, 26 were non-synonymous c hanges. Allelic frequencies of some of the polymorphisms were significantly different from those reported in European populations. For example, the Q5 06R substitution in the coagulation factor V gene, the so-called "Leiden mu tation", has a reported frequency of 2.3% in Europeans, but we detected the Leiden mutation in none of the Japanese genomes that we investigated. The allelic frequencies of the -33A>G SNP in the thrombomodulin gene were also very different; this allele occurred at a 12% frequency in the Japanese pat ients that we examined, although it had been detected in none of 82 Caucasi ans reported previously. These data support the hypothesis that some SNPs a re specific to particular ethnic groups.