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The Association Studies Of Xinjiang Han, Uygur Ischemic Stroke Infarction In Risk Factors Associated With Proprotein Convertase Subtilisin/Kexin9Gene

Posted on:2015-06-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:D F HanFull Text:PDF
GTID:1224330467972304Subject:Neurology
Abstract/Summary:PDF Full Text Request
Objective:1) Clinical data collected to explore the risk factors of Han, Uygurischemic stroke in Xinjiang;2) To analysis the association between proprotein convertasesubtilisin/kexin9(PCSK9) gene and Xinjiang Han, Uygur ischemic stroke;3) To Studythe interaction between PCSK9gene polymorphism and risk factors of Xinjiang Han,Uygur ischemic stroke. Methods: By adopting the method of case-control study, tocompare with the risk factors of Han, Uygur ischemic stroke in Xinjiang the Based on theprinciple of linkage disequilibrium, using the tag SNP (tagging-SNP, tSNP) strategyselection PCSK9gene18SNPs in, use SNaPshot genotyping platform and detectdimension, Han two national research object PCSK9gene polymorphism analysisPCSK9gene single nucleotide polymorphisms and Uygur, Han relationship betweenischemic stroke, using multivariate Logistic regression analysis you point and itsenvironmental factors on the role of ischemic stroke, and software applicationsHaploview4.2inference in order to find meaningful heliotype. By Logistic regressionanalysis methods to analyze the interactions between genetic polymorphisms of PCSK9gene and environment exposure to effects on ischemic stroke onset. Results:1) Twoethnic Chinese environmental risk factors for ischemic stroke ethnic differences exist.There are differences between Han ischemic stroke group and control group in Xinjiangregion, Hypertension, diabetes disease history, systolic and diastolic blood pressure,fasting plasma glucose levels, high-density lipoprotein cholesterol (HDL-C) andlow-density lipoprotein (LDL-C), which have statistical significance (P<0.05). Thereare differences between Uygur ischemic stroke group and control group in Xinjiangregion, Age, Hypertension, diabetes disease history, systolic and diastolic blood pressure, fasting plasma glucose levels, Cholesterol, high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein (LDL-C) and lipid poprotein (a), which have statisticalsignificance (P<0.05) The difference in age, systolic and diastolic blood pressure leveland lipid protein (a) between Han and Uygur ischemic stroke pateins was statisticallysignificant (P<0.05). The onset of Uygur ischemic stroke patients younger than the Hannationality (P<0.001). The systolic blood pressure, diastolic pressure and lipoprotein (a)levels of Uygur ischemic stroke patients were higher than the Han (P<0.05);2) PCSK9gene and ischemic stroke association analysis: there was difference between ischemicstroke group and control group in the genotype distribution of rs529787, the differencewas statistically significant (P<0.05). The genotype distributions and locus allelefrequency of rs529787andrs2479408were different in Han ischemic stroke group andcontrol group, the difference was statistically significant (P<0.05). The locus allelefrequency distributions of rs1711503were different in the Han case group and controlgroup, the difference was statistically significant (P<0.05). The genotype distributionsof rs2479413was different in Uygur ischemic stroke group and control group, thedifference was statistically significant (P=0.036). Building rs1711503and rs2479408haploid type found that relative to the G-C haploid type, the difference of type A-Chaploid between ischemic stroke group and the control group was statistically significant(P=0.011);3) To analysis interaction of PCSK9gene and ischemic stroke risk factorsbased on ethnic difference: the rs11583680(C/T), rs4927193(C/T) and rs693668(G/G)with low HDL levels exposure at the same time could increase the risk for ischemicstroke of Uygur observation object (OR values respectively:4.652,4.954,22.206). Thers10888896(C/G)、 rs529787(C/G) and rs572512(C/T) sites with hypertensionexposure at the same time could increase the risk for ischemic stroke of Uygurobservation object (OR values respectively:5.473、13.540、4.216、3.769). The rs529787(C/G) sites with diabetes mellitus exposure at the same time could increase the risk forischemic stroke of Uygur observation object (OR=18.994). the rs693668(G/A) sitesexposed to high LDL-C levels at the same time would reduce extra Han male observeobjects risk for ischemic stroke (OR=0.184). The rs483462(G/A) sites exposed to highTG levels at the same time would reduce extra Han male observe objects risk forischemic stroke (OR=0.482). The rs4927193(C/T) and rs2479413(T/T) sites with lowHDL-C exposure at the same time could increase the risk for ischemic stroke of Uygurmale observation object (OR values respectively:24.081、416.267). The rs7552841(C/T)sites with high TG exposure at the same time could increase the risk for ischemic stroke of Uygur male observation object (OR=7.380). The rs7552841(C/T) sites exposed to lowHDL-C levels at the same time, compared with C/C genotype would reduce extra Uygurmale observe objects risk for ischemic stroke (OR=0.052). The rs557435(G/A) sitesexposed to high TG levels at the same time would reduce extra Uygur male observeobjects risk for ischemic stroke (OR=0.398). The rs17111503(A/A), rs17111503(G/A),rs2479413(C/T) and rs693668(G/A) sites with hypertension exposure at the same timecould increase the risk for ischemic stroke of Uygur female observation object (ORvalues respectively:8.722、39.455、12.792、8.836). Conclusions:1) Hypertension,systolic blood pressure, fasting plasma glucose levels, HDL-C, LDL-C and lipidpoprotein (a) linked closely with the incidence of ischemic stroke in Xinjiang region. Age,systolic and diastolic blood pressure levels, lipoprotein (a) might be more related to theXinjiang Uighur population of ischemic stroke;2) The rs17111503and rs2479408PCSK9gene associated with ischemic stroke in China Han nationality. Carryingrs17111503-A and rs2479408-C allele would increased risk of ischemic stroke in ChinaHan nationality. The rs17111503and rs2479408A-C haplotype might be a geneticmarker of ischemic stroke in China Han nationality;3) There was interaction betweenPCSK9gene and the risk factors ischemic stroke. The interactions of the same gene withischemic stroke risk factors were different in different ethnic groups and different gender.
Keywords/Search Tags:Ischemic stroke, Proprotein convertase subtilisin/kexin9, Single nucleotide polymorphisms, Interaction analysis, ethnicity
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