The Relationship Between CETP-629C/A Polymorphism And Efficacy Of Atorvastatin Treatment With Coronary Heart Disease

ObjectiveTo investigate the relationship between CETP-629C/A polymorphism,serum Levels, lipid metabolism, and coronary heart disease(CHD) among the Chinese Han population of the Tianjin area; to study the the effete of gene variant of promoter region on transcription activity in vitro; Compared the therapeutic effect of torvastatin in different CETP genotype patients.Methods1. A hospital-based case-control study was conducted in Tianjin Chest Hospital from2010June to2011October. The subjects underwent angiography were divided into a case group (n=429) and a control group (n=275). The CETP gene promoter polymorphism at position-629was determined by restricted fragment length polymorphism using the polymerase chain reaction (PCR-RFLP) method. Meanwhile the serum CETP level was determined by enzyme-linked immunosorbent assay (ELISA) method.2. After Selecting CETP-629CC and-629AA homozygous gene, we obstained the target gene fragment at promoter region-745～+31bp by PCR.The product were ligated with pUCm-T vector to construct pUCm-T/-629CC and pUCm-T/-629AA recombinant plasmid. After use restriction enzyme to confirm the sequence, we ligated with pGL2-Basic to construct pGL2-CETP/-629CCand pGL2-CETP/-629AA recombinant plasmid.Use the technique of cation lipidosome transfection, recombinant plasmid was transfeceted into HepG2cells. After cells were cultured in vitro, collected the cells to detect the intensity of luciferase.3.Lipid levels were determined at basehne and following12weeks of treatment with20mg dose of atorvastatin in CHD patients, we compared the therapeutic effect of atorvastatin in different CETP genotype patients.Results1.The frequencies of-692A allele in the Tianjin Chinese-Han population was0.408, significantly lowerer than that in other domestic and foreign populations (0.479～0.701, P<0.05) 2.Variant AA genotype showed reduced CETP levels and higher HDL-C levels (P<0.05).compared to wild CC genotype.3. Although there was a negative trend correlation between serum CETP and HDL-C levels, it did not reach statistical significance (P>0.05)。4. There were significant differences in frequencies of-692genotypes and allele between the two groups(P<0.001), carries with CA/AA genotype and A allele showed higher risk of CHD, its OR (95%CI) were4.627(3.163～6.769).8.779(4.799～16.059) and3.173(2.453～4.104) respectively. There was no relationship between CETP-629C/A polymorphism and coronary artery stenosis degree.5. Logistic regression analysis revealed positive correlations between diabetes, smoking, higher serum levels of FBG. LDL-C、LP(a), lower serum HDL-C level, CETP CA/AA genetype and CHD.6. The AA genotype showed lower expression of luciferase reporter compared to the CC genotype in vitro (P<0.05)7. Compared with CA and AA genotype, CC genotype was shown to be associatedwith higher LDL-C、LP(a) reduction and HDL-C elevation in reponse to atorvastatin.ConclusionThe frequencies of allele and genotype of CETP-629in the Tianjin Chinese-Han population was significantly different from that in Other domestic and foreign populations. Variant AA genotype, which showed reduced CETP levels and higher HDL-C levels, is paradoxically associated with increased risk of CHD. Thus,CETP gene variation may affect coronary risk apart from the level of HDL-C.There was a negative trend correlation between serum CETP and HDL-C levels. The effect of atorvastatin therapy was associated with CETP-629genotype, CC genotype showed a better benefit of statin therapy.