Han Cholesteryl Ester Transfer Protein Cetp Gene Polymorphism Effects On Blood Lipids And Its Relationship With Type 2 Diabetes With Coronary Heart Disease

Backgroud and objectiveHigh density lipoprotein cholesterol is known by protective factors toatherosclerosis, Both genetic and environmental factors regulate HDL-C Levels,Heritability estimates ranged from 24% to 83%. Plasma cholesteryl ester transferprotein (CETP) facilitates the transfer of cholesteryl ester (CE) from high densitylipoprotein (HDL) to apolipoprotein B-containing lipoproteins. CETP is considered tobe a key protein in reverse cholesterol transport, Plasma CETP was importance inlipoprotein metabolism.CETP gene locus has been shown to determine the levels ofCETP and HDL-C and probably associate with CHD risk factors. We studied theTaq1B RFLP in the first intron of the CETP gene,levels of lipid profile and CETPmass in order to determine their association, we have also investigated the genotypeand allele frequencies of the polymorphism in patients with type 2 diabetesmellitus(DM) or coronary heart disease(CHD) in Han nationary.Predicting the clinicaltherapy of CHD.Design and methodThe genotypes of CETP Taq1B polymorphism were examined with the methodsof polymerase chain reaction(PCR) and restrictive fragment lengthpolymorphism(RFLP) in the samples of 103unrelated healthy individuals as controlgroup, 102 patients with type 2 DM(DM group), 123 patients with CHD(CHD group)and 104 patients with type 2 DM and CHD(DM+CHD group) in Chinese nationaryfrom Northern China. Enzyme-linked immunosorbent assay was used for themeasurement of CETP in human serum, Serum total cholesterol (TC) and TG levelswere determined with standard enzymatic colorimetric methods. Serum HDLcholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were determined withhomogeneous method. Concentrations of lipoprotein(a)[Lp(a)], apoA , apoAⅡ,apoB, apoCⅡ, apoCⅢ, apoE were measured by immunoturbidimetric assay. All calculations were performed using SPSS, version 11.5.ResultsThe levels of serum CETP were higher in CHD+DM group, CHD group and DMgroup than that in control group. Subjects in CHD group and in DM+CHD group hada lower serum levels of HDL-C compared with the controls.In our study, the frequency of the B1 and B2 allele of CETPTaq1B was around56.8% and 43.2%, respectively. The frequency of the allele was similar to thatreported in East Asians and in some European population.The distribution of of CETPTaq1B has no significant correlation with sex, CHD,hypertension, smoking, body mass index.The CETPTaq1B allele had significant correlation with serum HDL-C and CETP.Serum HDL-C levels were statistically lower (44.29 vs. 47.32, P=0.026) in subjectswho carried the B1 allele than in those who did the B2. CETP levels were higher insubjects who the B1 than the B2.The distribution of the CETP CETPTaq1B genotypes (B1B1, B1B2 andB2B2)and the frequency of B1 and B2 allele was 32.1%, 49.5%, 18.4%, 56.8%, 43.2%incontrols, 32.4%, 46.1%, 21.5%, 55.5%, 44.5% in DM group, 30.9%, 52.8%, 16.3%,57.3%, 42.7%in CHD group, 39.4%, 42.3%, 18.3%, 60.6%, 39.4% in DM+CHDgroup,respectively. B1 allele carriers had an increased low HDL-C risk(OR=1.662, 95%CI: 1.099～2.512). However, after adjustments for the well knownrisk factors such as sex,high LDL-C, high TG and smoking, this statistical differencedisappeared completely.Ages, smoking, hypertension,low HDL-C,low apoAⅠ,low apoCⅡwereindependent risk factors for CHD by logistic regression.ConclusionIn our study, we developed the methods of genome DNA extraction by NaI,CETPTaq1B polymorphism detection by PCR-RFLP, which are rapid and convenientfor large-scaled epidemiological screen, human biology research and clinical study in laboratory.The frequency of the CETPTaq1B polymorphism in the Chinese populationstudied is similar to that in other East Asians and some European population. Thegenetic effects of CETPTaq1B polymorphism on plasma HDL-C and CETPconcentration are confirmed in a Chinese population. Serum HDL-C levels werestatistically lower (44.29 vs. 47.32, P=0.026) in subjects who carried the B1 allelethan in those who did the B2. CETP levels were higher in subjects who the B1 thanthe B2.Frequency of C allele is not significant difference between DM and CHD andDM+CHD group and that of subjects in the control group, we could not confirm thatthe locus is an independent risk for CHD. Further studies need to be carried out todetermine if this polymorphism predicts clinical CHD events.