Identification of new single-nucleotide polymorphisms in the thrombin receptor gene and their effects on coronary artery diseases in Koreans

1. The thrombin receptor (the protease-activated receptor-1; PAR-1) is loca ted on vascular cells as well as platelets and may play important roles in atherosclerotic disorders, such as coronary artery diseases (CAD). In the p resent study, we searched for genetic polymorphisms of the PAR-1 gene and e valuated their effects on CAD by association analysis, 2. We identified six polymorphisms in the 5'-untranslated region of the PAR -1 gene by polymerase chain reaction-single-strand conformation polymorphis m (PCR-SSCP); five single-nucleotide polymorphisms (SNP) at -2355 (A to G), -2333 (T to G), -1428 (G to A), -1071 (C to T) and -561 (A to G) and a sim ple sequence repeat (SSR) polymorphism between -1935 and -1841. Five SNP we re in strong linkage disequilibrium with each other to make three major hap lotypes, the frequency of which was over 90% of all possible haplotypes. 3. For association analysis, 150 patients who had CAD (CAD+), 58 subjects w ho had no stenosis on the coronary angiogram and 186 reference subjects who had no clinical evidence of CAD were used from the Korean population, The genotype frequencies of the SNP were in Hardy-Weinberg equilibrium, except A-561G in CAD+. The association of these SNP as well as of the SSR with CAD was not evident. This result suggests no major roles of the PAR-1 gene in CAD in Koreans.