Abstract 2377: Genome-Wide Analysis for Coronary Spasm Utilizing GeneChip
Background: Coronary vasoconstriction has been recognized as an important factor in the progression of coronary artery disease. Disruption of the balance between coronary vasodilation and constriction, which predisposes patients to coronary spasm, could be related to low levels of vasodilation, high levels of vasoconstriction, or a combination of the two. We have shown that impairment of endothelium-dependent vasodilation may play a key role in the genesis of coronary spasm; however, the precise mechanism of the pathogenesis remains unclear. The prevalence of coronary spasm is higher in Japanese than in Caucasians, suggesting that genetic factors are involved in its pathogenesis. We performed a genome-wide case-control analysis for coronary spasm in Japanese women utilizing GeneChip.
Methods and Results: We did two screenings. All subjects in both screenings were diagnosed via an intracoronary injection of ACh while undergoing coronary angiography for chest pain, and had no significant coronary stenosis. Coronary spasm was defined as total or subtotal occlusion of the coronary artery with chest pain and ST changes. For initial screening, we genotyped 116,204 single nucleotide polymorphisms (SNPs) for 100 women (50 with coronary spasm; 50 controls) using the Affymetrix GeneChip 100K Set. For the 2nd screening, we performed case-control studies with 411 women (201 with coronary spasm; 210 controls) using 10 the lowest p value SNPs from the initial GeneChip screening. We found that the locus among the 10 SNPs, which is in Chr.14q21, was significantly associated with coronary spasm in women. We further analyzed the association of each haplotype with coronary spasm utilizing inferred haplotypes encompassing the locus for each subject. This analysis revealed that a haplotype was most strongly associated with coronary spasm and protective for coronary spasm. Multiple logistic regression analysis using classical risk factors and the locus showed that the locus was most significantly associated with coronary spasm (odds ratio= 0.35, p = 4.6×10-6).
Conclusions: We found that a genome-wide case-control analysis utilizing GeneChip is a useful method and that the locus in Chr.14q21 was associated with coronary spasm in Japanese women.