Objective We aim to investigate the polymorphism of Cholesteryl ester transfer protein (CETP) gene –629C/A among the coronary heart disease (CHD) Han population of the Tianjin area, to evaluate the influences of genetic factors on atorvastatin therapeutic effects and clinical outcomes in pharmacogenomics and provide theoretical basis for individual treatment.
Methods We studied 332 patients with angiographically confirmed CHD from October 2010 to July 2011 in the Tianjin Chest Hospital. The CETP gene promoter polymorphism at position –629 was determined by restricted fragment length polymorphism using the polymerase chain reaction (PCR-RFLP) method. Meanwhile the serum CETP levels was determined by enzyme-linked immunosorbent assay (ELISA) method. Lipid levels were determined at baseline and after 12 months of treatment with 20 mg/d atorvastatin in all patients. Clinical follow-up were performed for more than 1 year (range 12 to 23 months), major adverse cardiac events (MACE, including death, non-fatal infarction, revascularization, and stroke) were analysed. The Kaplan-Meier log-rank test was used to compare MACE-free survival between diffient genetypes.
Results 1. The frequencies of variant –692A allele was 0.408, AA genotype showed reduced CETP levels and higher HDL-C levels, compared to CC, CA genotype, it did not reach statistical significance (F = 0.893, P = 0.411 and F = 1.279, P = 0.282, respectively). Although there was a negative trend correlation between serum HDL-C and CETP levels, it did not reach statistical significance (r = –0.151, P = 0.081). 2. After 12months therapy of atorvastatin, CC genotype was shown to be associated with higher LDL-C, LP (a) reduction and HDL-C elevation in reponse to atorvastatin compared with CA and AA genotype. LDL-C levels decreased 35.4% in CC homozygotes, 18.84% in CA heterozygotes and 8.15% in AA homozygotes (P = 0.001). HDL-C levels increased 14.37% in CC homozygotes, 10.48% in CA heterozygotes and 6.64% in AA homozygotes, however the changes of HDL-C levels in three genotypes showed no significant difference (P = 0.470). 3. There was a 7.83% incidience of MACE after a mean follow-up of (18.66 ± 5.99) months, 3(0.90%) cases suffered death, 7(2.11%) cases non-fatal infarction, 13(3.92%) cases revascularization and 3(0.90%) cases stroke. The cumulative MACE free survival rates were 92.4%, 85.3% and 65.0% in CC, CA and AA genotypes, respectively (Log-rank P = 0.444).
Conclusions Our results suggest that variant AA genotype showed higher HDL-C levels and reduced CETP levels, however CC genotype show a better benefit of statin therapy associated with reduction in LDL-C and LP(a) levels, long-term clinical prognosis were not affected by three genotypes.
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