Relationship Between G1051A(R219K) Genetic Variationin Membrane Transporter ABCA1 And Blood Lipids Or Susceptibility Of Coronary Heart Disease

Relationship between G1051A(R219K)genetic variationin membrane transporter ABCA1 and blood lipids or Susceptibility of Coronary Heart DiseaseBACKGROUND AND OBJECTIVES Coronary atherosclerotic heart disease(CHD) is the most common type of organic pathological changes resulted fromatherosclerosis. To date, it has been shown that atherosclerosis is a typical andcomplicated disease influenced by genetic and environmental factors. People havelearned that adding the density of HDL-C may slow the progress ofatherosclerosis by and by. It is found in studies that ABCA1 is major membranetransporter involving metabolism of HDL-C. ABCA1 is an abbreviation of ATPbinding cassette transporter A1, which is of importance in the first step aboutHDL-C production. There are several sites of SNP (single nuclid polymorphism)in ABCA1 gene. It is reported that G1051A(R219K) polymorphism of ABCA1is associated obviously with plasma lipid levels and incidence of CHD inEuropean. This study is to observe the frequency of G1051A(R219K)polymorphism of ABCA1 about Han nationality in Beijing, and to associate thepolymorphism of ABCA1 gene with the level of blood lipids, susceptibility ofCHD and severity of the coronary artery branch lesions.METHODSA total of 178 patients in CHD and 83 unrelated healthy controlsubjects were included in our study. All patients were underwent coronaryarteriography and the number of branch lesions were identified. ABCA1 gene was 6首 都 医 科 大 学 硕 士 学 位 论 文genotyped by polymerase chain reaction and restriction fragment lengthpolymorphism methods (PCR/RFLP). Allele and genotype frequencies of theG1051A (R219K) polymorphism were compared between patients in CHD andhealthy control subjects. At the same time, the index of clinical and blood lipidsbiochemistry was compared between carriers of different genotype respectively.RESULTS The G1051A (R219K) variant allele frequency of the ABCA1 genewas 66.3% in the Han nationality in Beijing, and 41.9% in patients with CHD,P<0.05. The homozygous carriers of AA genotype in control group, one branchlesion group, two branch lesion group and three branch lesion group in CHD were53%, 23.6%, 22.0% and 17.2%, respectively. The difference was determinedbetween one branch lesion, two branch lesion and control subjects, P<0.05. Thesignificant difference was determined between three branch lesion and controlsubjects, P<0.01. The homozygous carriers of AA gene-type have lower level oftriglyceride ( 1.40±0.93 , 1.56±1.07mmol/L , P<0.05 ) and higher level ofhigh-density lipoprotein than homozygous carriers of GG gene-type(1.08±0.21,0.89±0.18mmol/L,P<0.01). The frequency of AA gene-type in CHD group islower than healthy people( 20.8% in CHD group VS 53.0% in control group,p<0.05),and the frequency of AA gene-type in three branch lesions group issignificantly lower than healthy people (17.2% in three branch lesions group VS53.0% in control group, p<0.01).CONCLUSION Our data suggests that the G1051A(R219K)polymorphism ofABCA1 is correlated not only with the level of blood lipids, but also with thesusceptibility of CHD and the severity of the coronary artery branch lesions. Thehomozygous carriers of AA gene-type have less susceptibility of CHD andnumber of coronary artery branch lesions.