Clinical Research On Association Of ABCG1 Single Nucleotide Polymorphisms With Essential Hypertension

Hypertension is one of the risk factors of cardiovascular and cerebrovascular diseases, with elevated blood pressure, the risk of stroke,myocardial infarction,heart failure and chronic kidney disease increases,causing huge losses to human health and social economy.Hypertension is a disease caused by environmental and genetic factors.Related data shows that nearly 40% of the blood pressure variation is due to genetic factors. Hypertension pathological process involves immune response,inflammatory response, insulin resistance, metabolic syndrome, the expression level of cell adhesion molecules, the expression of MCHC class II molecules, peptides or polysaccharide antigen,transcription and transportation in the process of gene expression.Korhor’s research of hypertension using the gene chips to explore the specific genetic expression found that the ABCG1 gene express lower in peripheral blood of patients with hypertension. The expression of the ABCG1 gene indicates that\ the gene may be associated with hypertension.ABCG1 encoding the ATP binding box protein plays an important role in the HDL synthesis and cholesterol reversal process. At present there is lack of research studying the association between ABCG1 protein and Essenial Hypertension. Does the ABCG1 gene in Jilin Area Han populations exist polymorphism? Does the ABCG1 gene Single Nucleotide Polymorphism relate to hypertension, dyslipidemia and other cardiovascular disease risk factors? This study which using molecular biology technology and quantitative genetics statistical methods is to explore the relationship between ABCG1 gene polymorphism and Essential hypertension, which is about to provides a brand new way for the clinical diagnosis and gene treatment.Objectives:1.Genotyping the ABCG1 gene Single Nucleotide Polymorphisms in Chinese Han population residing in Jilin Province;2.To investigate the genotypic and alleic distributions of ABCG1 in Chinese Han population residing in Jilin Province and determine the associations of the ABCG1 gene polymorphisms with EH;3.To explore the relationship between the ABCG1 gene polymorphisms and individual component of EH.Subjects and MethodsIn this study, we recruited 272 subjects with essential hypertension(EH) and 400age-and sex-matched normal subjects without diabetes mellitus.Height,weight, body mass index(BMI), systolic blood pressure(SBP), diasolic blood pressure(DBP),high density lipoprotein cholesterol(HDL-c), low density lipoprotein cholesterol(LDL-c),fasting blood glucose(FBG), triglyceride(TG), total cholesterol(TC), blood urea nitrogen(BUN), serum creatinine(SCr) were measured. The ABCG1 polymorphisms were detected using direct sequending and restriction fragment length polymorphism-polymerase chain reaction(RFLP-PCR).The relationship between ABCG1 SNPs and EH was determined.Results1.Clinical characteristics of the EH group and the control group: There were no significant differences in age, sex, height, weight, BMI, HDL-c, TC(P>0.05).Compared with control group, HR, LDL-c, TG, FBG, BUN(all of them: P<0.01) and SBP, DBP, MAP, SCr(all of them P<0.05) were significantly higher in EH group.2.PCR and sequencing results: out of all cases, control group were randomly selected from 100 specimens, a total of 200 cases, the intron 11 of ABCG1, 3 ’UTR region were direct sequencing, found seven single nucleotide polymorphisms(SNPs),respectively rs11700907(A→C)、rs727791(T→G)、rs2234721(G→T),rs7275482(C→T),rs4920081(C→T)、rs4920080(C→T)、rs1044317(A→G) and from NCBI gene bank of ABCG1 corresponding sites entirely consistent. All of these SNPs is verified.3.Rs727791(T→G)、rs2234721(G→T),rs7275482(C→T),rs4920081(C→T)、rs4920080(C→T)、rs1044317(A→G)seven locus in primary hypertension group and control group, the frequency distribution did not deviate from the hardy Weinberg equilibrium, the selection of the genotype of sample can genetic stability,can represent the whole group.4.The SNPs and essential hypertension(1) Rs1044317: three genotypes AA, Ag, GG genotype frequency distribution difference between the two groups was statistically significant(EH group AA for18.68% Ag 38.10%, GG 43.22%; control group AA 38.25 AG was 37.50%, GG was24.25%, X2=12.79, P < 0.05) that primary high blood pressure and rs1044317 this SNP in the mutations associated with. And two groups of gene frequency distribution with significant difference.(2) Rs1179907: three genotypes AA, AC, CC genotype frequency distribution difference between the two groups was statistically significant(EH group AA to29.67%, AC is 44.69% CC 25.64%; control group AA for 49.25, AC 37.75% CC is13.00%, X2=15.79, P < 0.05) that primary high blood pressure and rs1179907 this SNP in the mutations associated with. And two groups of gene frequency distribution with significant difference.(3) Rs727791: three genotype TT, TG and GG genotype frequency distribution of the difference between the two groups was statistically significant(EH group, TT was 12.82%, TG 47.25%, GG for 39.93%; 27.25% in the control group, TT, TG was42.25%, GG was 35.19%, X2=20.9, P < 0.05) that primary high blood pressure and rs727791 this SNP in the mutation is associated.(4) Rs7275482: three genotypes CC, CT, TT genotype frequency distribution difference between the two groups was statistically significant(EH group CC is37.73% for CT 46.52%, TT was 17.58%; control group CC was 53.75%. CT is40.25% CC 6.00%, X2=15.80, P < 0.05) that primary high blood pressure and rs7275482 this SNP in the mutations associated with. And two groups of gene frequency distribution with significant difference.(5) The remaining SNPS showed no significant difference between EH and controls(P>0.05).Conclusion:1.Direct sequencing found ABCG1 gene in intron 11 sub rs11700907(a > C) exists in Chinese Han population in Jilin Province, rs727791(T > G), rs2234721(g, t),rs7275482(C- > t), rs4920081(C- > t), rs4920080(C- > t), gene polymorphism exists in the 3 ’UTR region rs1044317(a to g).2.Rs1044317(A, G), rs11700907(A, C), rs727791(T, G), rs2234721(G, T) alleles are independent risk factors for EH.