eNOS基因多态性与贵州汉族、苗族、布依族原发性高血压的相关性研究

发布时间：2018-01-29 02:41

本文关键词： 原发性高血压一氧化氮合酶基因多态性贵州少数民族　出处：《贵州医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:探讨贵州汉族、苗族、布依族人群eNOS基因上3个SNP位点(启动子区rs2070744、第7外显子rs1799983、14内含子rs3918181)及1个VNTR位点(第4内含子27bp VNTR)的多态性与原发性高血压(essential hypertension,EH)的关系。方法:选取贵州地区EH患者456例(汉族195例、苗族127例、布依族134例)和体检健康者453例(汉族206例、苗族111例、布依族136例)为研究对象,所有EH患者均符合2010年中国高血压防治指南的标准,收集身高、体重等相关临床资料,测定总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)、空腹血糖、尿酸(Uric acid,UA)。采用Taq-Man MGB探针法对上述研究对象eNOS基因rs2070744、rs1799983、rs3918181等SNP位点进行基因分型;采用PCR及琼脂糖凝胶电泳检测27bp VNTR的多态性,并对所有研究位点进行DNA测序验证,分析各位点不同基因型与EH的关系。采用Logistic回归分析EH发病的危险因素,P0.05为差异有统计学意义。结果:(1)贵州汉族、苗族、布依族人群eNOS基因位点rs2070744、rs1799983、rs3918181及27bp VNTR的多态性分布在EH组与对照组中均符合Hardy-Weinberg平衡。(2)贵州人群EH患者年龄、体重指数(Body Mass Index,BMI)、空腹血糖、TG与对照组相比存在统计学差异。按民族分层后,汉族与布依族EH组中年龄、BMI、空腹血糖、TC、TG高于对照组;苗族EH组中年龄、BMI、空腹血糖高于对照组;各民族两组相比,差异均有统计学意义(P0.05);Logistic回归分析校正年龄、BMI、临床指标等混杂因素后,结果提示年龄、空腹血糖可能是汉族EH的独立危险因素;年龄、BMI、空腹血糖可能是苗族和布依族EH的独立危险因素。(3)贵州人群EH组eNOS基因rs2070744、rs1799983、rs3918181和27bp VNTR的基因型频率和等位基因频率与对照组之间差异无统计学意义(P0.05);按民族分层后,3个民族EH组eNOS基因上述4个多态位点基因型频率和等位基因频率与对照组之间差异无统计学意义(P0.05)。(4)rs1799983位点基因型频率及等位基因频率在汉族与布依族之间及苗族与布依族之间分布差异有统计学意义(P0.05);27bp VNTR基因型频率及等位基因频率在汉族与苗族之间分布差异有统计学意义(P0.05);rs2070744位点、rs3918181位点基因型频率及等位基因频率在3个民族之间分布差异无统计学意义(P0.05)。(5)贵州人群中rs2070744位点与27bp VNTR位点间存在强连锁不平衡。(6)经Haploview4.1软件对贵州人群eNOS基因rs2070744、27bp VNTR、rs1799983和rs3918181等4个位点构建单倍型并分析,单倍型T-b-G-G、T-b-G-A所占比例较高,所有的单倍型组合在EH组与对照组间差异无统计学意义(P0.05)。结论:(1)eNOS基因rs2070744、rs1799983、rs3918181、27bp VNTR等4个位点多态性与贵州地区汉族、苗族、布依族EH的发生可能不具有相关性;4个位点构建的单倍型可能与贵州人群EH不相关。(2)eNOS基因rs1799983、27bp VNTR等两个位点基因型频率及等位基因频率分布在汉族、苗族、布依族人群之间有差异,rs2070744、rs3918181位点基因型及等位基因频率分布在贵州苗族、布依族、汉族人群之间无差异。(3)年龄、BMI、空腹血糖、TC和TG可能是贵州人群EH的易患因素,Logistic回归分析提示年龄、BMI、空腹血糖可能是贵州人群EH的独立危险因素。(4)贵州人群中rs2070744位点与27bp VNTR位点间存在强连锁不平衡。
[Abstract]:Objective: To investigate the Guizhou Han, Miao, Buyi people on the eNOS gene of 3 SNP loci (promoter rs2070744, exon seventh rs1799983,14 intron rs3918181) and 1 VNTR loci (fourth 27bp intron VNTR) the polymorphism and essential hypertension (essential, hypertension, EH). Methods: the relationship between Guizhou selected 456 EH patients (195 cases of Han, Miao and Buyi in 127 cases, 134 cases) and 453 cases of healthy subjects (111 cases and 206 cases of Han, Miao, Buyi and 136 cases) as the research object, all EH patients were consistent with the 2010 guidelines for prevention and treatment of high blood pressure Chinese standard, collect relevant clinical height. Weight determination of total cholesterol (Total, cholesterol, TC), triglycerides (Triglyceride, TG), fasting blood glucose, uric acid (Uric, acid, UA). Using Taq-Man MGB probe method rs1799983 on the research object of eNOS gene rs2070744, rs3918181, SNP genotyping; The polymorphism of PCR and agarose gel electrophoresis of 27bp VNTR, and DNA sequencing of all research sites, to analyze their relationship between different genotypes of EH. Logistic regression was used to analyze the risk factors of EH P0.05, the difference was statistically significant. Results: (1) Guizhou Han, Miao, Buyi people eNOS gene loci rs2070744, rs1799983, rs3918181 and 27bp polymorphism of VNTR in EH group and control group were consistent with the balance of Hardy-Weinberg. (2) EH in Guizhou population with age, body mass index (Body Mass, Index, BMI), fasting blood glucose, TG compared with the control group. There were significant differences in ethnic stratification, age, Han nationality and Buyi group EH BMI, fasting blood glucose, TC, TG higher than the control group; EH group in age, Miao BMI, fasting blood glucose was higher than the control group; the two ethnic group compared, the differences were statistically significant (P0.05); Logistic regression analysis Adjustment for age, BMI, clinical indicators and other confounding factors, the results showed that age, fasting blood glucose may be an independent risk factor for EH in Han population; age, BMI, fasting blood glucose may be independent risk factors of Miao and Buyi EH. (3) Guizhou group EH eNOS gene rs2070744, rs1799983, there was no significant difference between rs3918181 27bp and VNTR genotype and allele frequencies and the control group (P0.05); according to the national stratification, between the 3 ethnic group EH eNOS gene of the 4 polymorphic loci genotype and allele frequencies between control group and the difference was statistically significant (P0.05). (4) rs1799983 genotype the frequency and allele frequency between Han nationality and Buyi and Miao and Buyi distribution difference was statistically significant (P0.05); 27bp VNTR genotype and allele frequencies in the Han and Miao nationality between the distribution difference was statistically significant (P0.05); rs2070744 locus, rs3918181 genotype frequency and allele frequency distribution in the differences between the 3 ethnic groups had no statistical significance (P0.05). (5) in Guizhou population rs2070744 locus and 27bp locus VNTR has strong linkage disequilibrium. (6) by Haploview4.1 software of rs2070744,27bp VNTR eNOS gene in Guizhou population. Rs1799983 and rs3918181 4 loci and haplotype construction analysis, haplotype T-b-G-G, T-b-G-A accounted for a higher proportion, there was no significant difference in all the haplotype combination between EH group and control group (P0.05). Conclusion: (1) eNOS gene rs2070744, rs1799983, rs3918181,27bp Han, VNTR 4 polymorphism and Guizhou area Miao, Buyi and occurrence of EH may not have the correlation; 4 loci haplotypes were constructed may not be associated with EH in Guizhou population. (2) eNOS gene rs1799983,27bp VNTR two locus genotype frequency and allele The gene frequency distribution in the Han, Miao, Buyi people have differences between rs2070744 rs3918181 genotype and allele frequency distribution in Guizhou Miao, Buyi, no difference between Han population. (3) age, fasting blood glucose, BMI, TC and TG may be risk factors for Guizhou EH group. Logistic regression analysis showed that age, BMI, fasting blood glucose may be independent risk factors of EH in Guizhou population. The population of Guizhou (4) in rs2070744 site and 27bp site of VNTR between the strong linkage disequilibrium.

【学位授予单位】：贵州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R544.11

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