Abstract 1782: Prediction of Genetic Risk for Myocardial Infarction in Japanese Individuals
Introduction. Although the recent genetic association studies have implicated several genes in predisposition to myocardial infarction (MI), the genes that contribute to genetic susceptibility to MI have not been fully elucidated.
Hypothesis. We assessed the hypothesis that new genetic variants that confer susceptibility to MI in Japanese individuals might be identified by a genome-wide association study.
Methods. The study population comprised 5014 Japanese individuals, including 1444 subjects with MI and 3570 controls. The 150 polymorphisms were selected by the genome-wide association studies of MI and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). The genotypes for these polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.
Results and Conclusions. An initial screen by the chi-square test revealed that the A/G polymorphism of SEMA3F (rs12632110), the C/T polymorphism of CLEC16A (rs9925481), the A/G polymorphism of LAMA3 (rs12373237), and the C/G polymorphism of PCSK2 (rs6080699) were significantly (false discovery rate of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the A/G polymorphism of SEMA3F (P =0.0015; odds ratio, 0.76), the C/T polymorphism of CLEC16A (P =0.0010; odds ratio, 0.75), the A/G polymorphism of LAMA3 (P =0.0128; odds ratio, 0.80), and the C/G polymorphism of PCSK2 (P =0.0151; odds ratio, 1.19) were significantly (P <0.05) associated with MI. A stepwise forward selection procedure also revealed that these polymorphisms were significant (P <0.05) and independent determinants of MI. In conclusion, genetic variants of SEMA3F, CLEC16A, LAMA3, and PCSK2 were significantly associated with MI in Japanese individuals. Determination of genotypes for SEMA3F, CLEC16A, LAMA3, and PCSK2 may prove informative for prediction of the genetic risk for MI in Japanese individuals.