Abstract 1400: Genetic Risk for Myocardial Infarction in Japanese Individuals With or Without Chronic Kidney Disease
Introduction. Although chronic kidney disease (CKD) is a serious clinical problem in that individuals with CKD are at increased risk for myocardial infarction (MI), genetic variants that confer susceptibility to MI in individuals with or without CKD have remained unknown.
Hypothesis. We assessed the hypothesis that genetic variants that confer susceptibility to MI might differ between individuals with CKD and those without this condition.
Methods. A total of 4344 individuals from two independent populations was examined. Subject panel A comprised 3097 individuals without CKD, including 833 subjects with MI and 2264 controls; and subject panel B comprised 1247 individuals with CKD, including 506 subjects with MI and 741 controls. The 150 polymorphisms examined in this study were selected by genome-wide association studies of MI and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix).
Results and Conclusions. In subject panel A, an initial screen by the chi-square test revealed that the C/T polymorphism of CLEC16A (rs9925481) and the A/G polymorphism of LAMA3 (rs12373237) were significantly (false discovery rate of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the C/T polymorphism of CLEC16A (P=0.0003; odds ratio, 0.66) and the A/G polymorphism of LAMA3 (P=0.0087; odds ratio, 0.75) were significantly associated with MI. A stepwise forward selection procedure also revealed that these polymorphisms were significant and independent determinants of MI. In subject panel B, the chi-square test revealed that the A/G polymorphism of LLGL2 (rs1671021), the C/T polymorphism of POLR1D (rs14105), and the A/G polymorphism of TSPAN9 (rs2011973) were related (P ≤0.005, false discovery rate of ≤0.25) to MI, but none of these polymorphisms were significantly associated with this condition. In conclusion, genetic variants that confer susceptibility to MI differed between individuals with CKD and those without this condition. Determination of genotypes for CLEC16A and LAMA3 may prove informative for assessment of the genetic risk for MI in Japanese individuals without CKD.