| Background and purpose:The cerebrovascular disease(mainly for stroke)become the highest incidence of all the diseases that has more than the incidence of cancer in China,and the main types of stroke is ischemic stroke(IS),IS accounts for more than 80% of incidence of stroke.IS is caused by the interaction of around environmental and genetic factors.ATP binding transporter A1/G1(ABCA1/G1)are the key transporters mediated cholesterol efflux from cell,their main function is to mediate the flow of cellular phospholipids and cholesterol,phospholipids and cholesterol will be binding to apolipoprotein A-I on cell surface,then mature high density lipoprotein protein(HDL)will form,thus starting the process of reverse cholesterol transport(RCT)of excess cholesterol excreted.The study found that ABCA1/ABCG1 play an important role in reducing lipid levels in macrophages,especially cholesterol,and then to prevent the formation of foam cells,and foam cells are important pathophysiological phenomena in the development of atherosclerosis(AS).Tomio,Umemoto et al found thatapolipoprotein A1 and HDL depend on ABCA1 / ABCG1 of the surface of adipocytes have anti-inflammatory effects,It has been proved that ABCA1/ABCG1 play an important role in the development of inflammation while regulating the homeostasis of lipid metabolismboth,whether in macrophages,endothelial cells,or in adipocytes.Therefore,this study investigated the polymorphisms of the two genes,ABCA1 and ABCG1,its correlation was analyzed with ischemic stroke and blood lipid related metabolic markers in northern Han Chinese population.Research object:1.1 Selection of IS patientsIn the First Affiliated Hospital of Zhengzhou University and the first people’s Hospital of Zhengzhou,neurology department was randomly selected from IS patients who were hospitalized from March 2011 to September 2016: a.The screening population included: IS patients were 220 cases,including 136 males,the ratio was 61.8%,female 84 cases,the average age was 62.2 ± 10.4 years old.b.The validated population included: 227 patients with IS,including 156 males,the ratio was 68.7%,females 71 males,with an average age of 58.4 ±12.1 years.1.2 Selection of normal control individualsRandomly selected individuals within the same period of IS group physical examination,gender and age matched,and no cerebral hemorrhage,cerebral embolism,cerebral infarction and other individuals as control group.The primary screening population: 206 cases,including male(n=117,56.8%)and female(n=89),with an average age of 63.6±10.5 years old.The verify group: 227 cases,including male(170,74.9%)and female(n=57),with an average age of 60.3±14.8 years old.All of the participants were all Han people in Henan and were not related to blood.This study was approved by the ethics committee of Zhengzhou University,and all participants signed informed consent.1.3 Selection of loci10 tag SNPs loci---rs1378577,rs1800977,rs1800978,rs1893590,rs2230806,rs2230808,rs4149338,rs4149339,rs57137919,and rs363717 were identified by searching,screening,and identifying feasible.Method:Select rs1378577,rs1800977,rs1800978,rs1893590,rs2230806,rs2230808,rs4149338,rs4149339,rs57137919,rs363717 and other 10 loci in the screening population using Kompetitive Allele-Specific PCR,the competition of allele specific PCR(KASP)technology for genotyping accuracy,the use of Sanger 测 序 technology to verify the KASP;positive loci,rs57137919 and rs2230808 expanded samples were verified;the expression level of ABCA1 and ABCG1 in peripheral blood by using real-time quantitative Q-PCR that detected m RNA of IS group and normal control group.Result:1.In the high cholesterol group,rs57137919G>A allele frequency of A is 17.5% in IS group was lower than that in control group 26.5%(P=0.018<0.05).A allele carriers,the risk of IS was significantly lower(OR=0.590,95%CI:0.380-0.919).The dominant genetic frequency of AA+AG is 32.5% were significantly lower than the control group 44.7%,and the difference was significant(P=0.045).Individuals with AA+AG have a lower risk of developing IS(OR=0.594,95%CI:0.355-0.993).2.In the high cholesterol group,rs2230808G>A allele frequency of A is 26.6% in the IS group was significantly lower than the control group 35.1%(P=0.041<0.05).A allele carriers,the risk of IS was significantly lower(OR=0.671,95%CI: 0.457-0.986).Frequency of AG genotype is 32.5% in IS group is significantly lower than the control group 50.1%(P=0.003<0.05).Individuals with AG have a lower risk of developing IS(OR=0.452,95%CI:0.266-0.768).The dominant genetic frequency of AA+AG genotype is 32.5% in IS group was significantly lower than the control group 44.7%(P=0.045<0.05).Individuals with AA+AG have a lower risk of developing IS(OR=0.594,95%CI: 0.355-0.993).3.Haplotype analysis showed that the G+G haplotype of rs2230808+rs57137919,the frequency of 63.2% in the IS group was significantly higher than that of control group 47.2%,the difference was significant(P=0.00).G+G is risk haplotype of IS(OR=1.924,95%CI:1.350-2.741),G+A haplotype of rs2230808+rs57137919,the frequency of 10.2% in IS group less than 17.6% in the control group,the difference was significant(P< 0.05).G+A haplotype of rs2230808+rs57137919 is a protective factor for IS(OR=0.530,95%CI:0.305-0.919)..4.The m RNA expression level of ABCG1 gene in the IS group(2.08 ± 1.98)was significantly higher than that in the control group(1.27 ±0.65),and the difference was statistically significant(P<0.05).5.The mRNA expression level of ABCA1 gene in group IS(1.69 ± 1.22)was not significantly higher than that of the control group(1.31 ±0.89),and the difference was not statistically significant(P>0.05).Conclusion:1.The A allele of rs57137919 in the ABCG1 promoter region may be a protective factor of IS,and its polymorphism may be involved in the regulation of ABCG1 expression.2.The A allele of rs2230808 in the ABCA1 exon region may be a protective factor for IS.3.Haplotype G+G may be a risk factor for IS,while G+A may be a protective factor for IS. |
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