The APJ Receptor A445C C Mutant Carrier Improves HDL Metabolism in Korean CVD Patients

Backgrouds: The apelin/APJ receptor system plays a mediator of CVD, but its molecular mechanisms related to APJ receptor polymorphism on HDL metabolism in CVD patients remains unclear. Methods: 386 CVD outpatients were screened by dyslipidemia (DYS; TG>150 mg/dl and HDLc<40 for men, <50 mg/dl for women) and non-DYS, and biomarkers for HDL metabolism and APJ receptor A445C polymorphisms (SNP rs948847) were examined. Results: BMI, insulin, HOMA-IR, TC, TG, LDLc, leptin, visfatin, and IL-6 levels were higher as well as adiponectin and HDL peak sizes were lower in DYS than those of non-DYS. High apelin levels were related to lower TC and LDL, and higher adiponectin and leptin levels. Increasing apelin was associated with higher TG and lower HDL in DYS, not in non-DYS. However, APJ A445C C mutant carrier, 5.7% frequencies among CVD, has protective effects in DYS. We found that lower TG/HDL, insulin, HOMA-IR, and visfatin levels and higher adiponectin levels in DYS with C allele compared to DYS with A allele, in spite of high apelin (>231 pg/mL) status. Decreasing TG/HDL in DYS with C allele was strongly improved with HDL metabolism such as increasing HDL with HDL2b and decreasing TG with HDL3 subtypes. Even though there were no changes in the mass of RCT enzymes between the A and C alleles in high apelin group, they were closed to those of non-DYS. Conclusion: Hyperapelinemia was associated with DYS risks compared to non-DYS, but APJ mutant carrier may have the beneficial effects of the HDL metabolism in the developments of DYS in Korean CVD patients.