Effect of CETP Polymorphism on Atorvastatin Lipid-Regulating Effect and Clinical Prognosis of Patients with Coronary Heart Disease
Guo-Long Gu, Xiao-Lin Xu, Qing-You Yang, Ruo-Long Zeng
Department of Cardiovascular Medicine, Jiangyin Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine Affiliated Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin, Jiangsu, China (mainland)
Med Sci Monit 2014; 20:2824-2829
The aim of this study was to investigate the influence of genetic polymorphism of cholesteryl ester transfer protein (CETP) gene polymorphism –629C/A on the therapeutic effect of atorvastatin and clinical outcome in Han Chinese patients with coronary heart disease (CHD).
Material and Methods: From October 2011 to December 2012, 348 patients with angiographically confirmed CHD were recruited. CETP gene polymorphism was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method. Serum level of CETP was determined with enzyme-1inked immunosorbent assay (ELISA). Lipid 1evel in all patients was determined at baseline and after 12 months of treatment with 20 mg/d of atorvastatin. All the patients were followed-up at least 12 months. Major adverse cardiac events, including death, non-fatal infarction, revascularization, and stroke (MACE), were recorded.
Results: The frequency of the –629A allele was 0.412. Compared with CC or CA genotypes, individuals with AA genotype had lower CETP levels (P=0.026) and higher high-density lipoprotein cholesterol (HDL-C) levels (P=0.035). After 12 months of atorvastatin therapy, carriers with CC genotype had greater reduction of low-density lipoprotein cholesterol (LDL-C) (P<0.001), reduced LP (a) (P=0.005), and elevated HDL-C (P=0.045) compared with CA or AA genotypes. The incidence of MACE after a mean follow-up of 17.3±5.2 months was 8.8%. The cumulative MACE-free survival rates were 90.1%, 85.2%, and 71.1% for CC, CA, and AA genotypes, respectively.
Conclusions: Our results suggest that the AA variant of the –629A allele of CETP gene had higher HDL-C levels and reduced CETP levels, but patients with CC genotype appeared to have benefited more from statin therapy with reduction in LDL-C and LP (a) levels. Long-term clinical prognosis was, however, not affected by the 3 genotypes.
Keywords: China - epidemiology, Cholesterol Ester Transfer Proteins - genetics, Coronary Artery Disease - mortality, Follow-Up Studies, Genetic Predisposition to Disease, Heptanoic Acids - therapeutic use, Hypolipidemic Agents - therapeutic use, Lipids - blood, Polymorphism, Single Nucleotide - genetics, Prognosis, Pyrroles - therapeutic use, Survival Rate