Effects Of ABCA1 Gene Polymorphisms On Risk Factors,Susceptibility And Severity Of Coronary Artery Disease

Objective: The aim of the study was to investigate the effects of the rs1800976,rs4149313 and rs2230806 polymorphisms in ATP binding cassette transport protein A1(adenosine triphosphate-binding cassette transporter A1,ABCA1)gene on risk factors,susceptibility and severity of coronary artery disease(CAD)in Chinese Han population.Methods: Six hundred and fifty-nine patients who were suspected of CAD and accepted coronary angiography examination at the Department of Cardiology,Affiliated Hospital of North Sichuan Medical College(Nanchong,China)were enrolled in the study between December 2015 to December 2018.Among these subjects,442 subjects were divided into CAD group(male 281,female 161,median age 64.60 ±9.30),while the rest two 217 subjects were divided into control group(male 120,female 97,median age 61.21±10.06).The physiology and biochemistry data of all these paticipants were collected.Genome DNA was extracted from peripheral blood leucocytes and the genotypes of the ABCA1 rs1800976,rs4149313 and rs2230806 polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism method.The severity of CAD was evaluated by Gensini score system,number of diseased coronary branches and extent of coronary stenosis.Results:(1)The allele and genotype frequencies of rs1800976 polymorphism were significantly different between CAD group and control group(p<0.05),and the C allele of rs1800976 polymorphism was found to be a risk allele for CAD.(2)The allele and genotype frequencies of rs4149313 polymorphism were significantly different between CAD group and control group(p<0.05),and the G allele of the rs4149313 polymorphism was found to be a risk allele for CAD.(3)The allele and genotype frequencies of rs2230806 polymorphism were significantly different between CAD group and control group(p<0.05),and the A allele of rs2230806 polymorphism was found to be a risk allele for CAD.(4)In CAD group,C allele of the rs1800976 polymorphism was significantly associated with high levels of hypersensitive C-reactive protein(hs-CRP)and cystatin c(CysC),and its frequency increased with percentiles of Gensini scores,number of diseased coronary branches and extent of coronary stenosis(P < 0.05 for all).(5)In CAD group,the patients with GA genotype of the rs4149313 polymorphism had higher levels of total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),apolipoprotein B and hs-CRP than those with AA genotype(P < 0.05 for all);in control group,the subjects with GA genotype of the rs4149313 polymorphism had higher levels of hs-CRP than those with AA genotype(P < 0.05).(6)In CAD group,The subjects with AA genotype of the rs2230806 polymorphism had higher levels of TC,LDL-C and uric acid(UA)than those with GA genotype(P < 0.05 for all).(7)No associations between the rs4149313 or rs2230806 polymorphism and severity of CAD were detected.Conclusion:(1)The rs1800976 polymorphism of ABCA1 gene was significantly associated with the occurrence and severity of CAD,which is possibly mediated by hs-CRP and CysC.(2)The ABCA1 rs4149313 polymorphism had significant effects on serum lipid levels,and which is associated with the occurrence of CAD.(3)The ABCA1 rs2230806 polymorphism had significant effects on serum lipid levels,and which is associated with the occurrence of CAD.