The apolipoprotein A5 -1131T>C promoter polymorphism in Koreans: Association with plasma APOA5 and serum triglyceride concentrations, LDL particle size and coronary artery disease

Background: The association between -1131T>C single nucleotide polymorphism (SNP) of the apolipoprotein A5 gene (APOA5) and hypertriglyceridemia raised the possibility that this SNP could be related to coronary artery disease (CAD) risk. Therefore, we investigated the association of this APOA5 -1131T>C SNP with circulating concentrations of APOA5, triglyceride and CAD in Koreans. Methods: CAD patients (n = 741) and age-, sex-matched healthy controls (n = 741) were genotyped for the APOA5 -1131T>C SNP. The main outcome measures were the odds ratio (OR) on CAD risk and lipid variables, APOA5 concentration and LDL particle size. Results: The presence of the minor allele at the -1131T>C SNP was associated with an increased risk of CAD [OR 1.34 (95% CI, 1.09-1.65), P = 0.007] after adjusting for BMI, alcohol consumption, systolic blood pressure and diastolic blood pressure. There was an association between the APOA5 concentration and the -1131T>C genotype in controls (T/T: 245 ± 7 ng/ml, T/C: 220 ± 6, C/C: 195 ± 12; P = 0.001) and CAD patients (T/T: 218 ± 8 ng/ml, T/C: 185 ± 7, C/C: 169 ± 12; P < 0.001). Subjects with T/C or C/C in control and CAD patient groups showed higher triglyceride than those with T/T genotype. Also, the -1131T>C polymorphism was associated with LDL particle size (P = 0.003), with the T/C or C/C controls having smaller size than the T/T controls. Conclusions: The APOA5 -1131C allele is associated with reduced APOA5 concentration and with increased CAD risk. This is consistent with the observed association between the -1131C SNP, increased triglycerides as well as small LDL particle size.