Study On The Association Of Single Nucleotide Polymorphisms Of The Cholesteryl Ester Transfer Protein Gene With Coronary Heart Disease

Objective: To explore the influencies of TaqIB polymorphism, -629A/C polymorphism and D442G mutation in the cholesteryl ester transfer protein (CETP) gene on serum lipids , apoliproteins and CETP concentration, and essential association with coronary heart disease.Methods: Samples of peripheral blood white cell were extracted among 128 patients with CHD, and 247 unrelated controls,all of Chinese Han nationality. The variations of CETP gene were determined by PCR-RFLP and subsequent agarose or polyacrylamide gel electrophoresis. Automated Biochemical Analyzer was used to measure the serum total cholesterol(TC), triglyceride(TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol (HDL-C) , apolipoprotein AI(ApoAI) and apolipoprotein(ApoB).The CETP concentration was determined using ELISA. The association between the CETP gene and CHD was analyzed by using multivariate logistic regression models.Results: (l)The allele A frequencies of TaqlB polymorphism in human CETP gene for control group and patients with coronary heart disease were 0.53, 0.65 respectively. Compared with the control group, the frequencies of the B1 allele in CHD group was significantly higher(P<0.05).In each group, the serum CETP concentration and LDL-C levels was significantly higher in B1B1 genotype than in B2B2 genotype, but it was significantly lower for HDL-C levels(P<0.05). (2) For the -629A/C polymorphism, the frequencies of C allele in the controls and CHD group were 0.45,0.56 respectively. The frequencies of the C allele in CHD group was significantly higher than in controls(P<0.05). In the same group, the serum CETP concentration was significantly higher in B1B1 genotype than in B2B2 genotype, but it was significantly lower for HDL-C levels(P<0.05).(3) For D442G mutation, GG genotype was not detected in the two groups. The frequencies of D442G mutation in controlsand cases were 0.06,0.04 respectively and had no significant difference between two groups. (4)After adjustment for major confounders including age, gender and body mass index, multiple logistic regression analysis show that :(1)The B1B1 genotype of CETP TaqlB polymorphism increased the risk of coronary heart disease significantly (OR=3.18, 95%CI:1.44-7.05).(2) The -629A/C polymorphism in CETP gene was not in association with CHD significantly(OR= 1.86,95% CI: 0.89-2.17). (3)The D442G mutation in CETP gene was not in association with CHD significantly(OR=0.87,95% CI: 0.75-1.82). (4)There was a significantly higher risk for CHD in the haplotypes for BIB 1 genotype and CC genotype , compared with the other haplotypes between the two SNPs.Conclusion: The allele frequencies of TaqlB polymorphism in human CETP gene were significant difference in different ethnic groups. The genetic variation at the CETP gene locus are both associated with serum HDL-C levels and CETP concentrations to a certain degree. The TaqlB B1 allele displayed higher CETP concentrations and lower HDL-C levels than B2 allele;-629C allele displayed higher CETP concentrations and lower HDL-C levels than A allele(P<0.05).The TaqlB and -629A/C polymorphisms may be highly correlated with coronary heart disease. The Bl allele and the C allele may be independent risk factors for CHD. CETP gene may be one of the genetic candidate genes for coronary heart disease among Chinese Han population.