【作者】 姚超永；

【导师】 尹雪艳；

【作者基本信息】 大理学院 ， 内科学， 2011， 硕士

【摘要】 [目的]研究血管紧张素原(angiotensinogen, AGT)基因核心启动子区A-6G多态性与大理地区白族人群原发性高血压之间的关系。[方法]以大理地区67例白族原发性高血压患者(高血压组)和54例健康体检者(对照组)为对象进行研究。从所有研究受试者外周静脉抗凝血中提取DNA,采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP)方法进行基因分型,随机选取部分标本用双向荧光测序进行基因分型验证；用SAS 9.13软件进行统计分析,研究AGT基因核心启动子区A-6G多态性与白族人群原发性高血压之间的关系。[结果](1)研究发现白族人AGT基因核心启动子区-6位点存在A/G多态性。(2)高血压组与对照组相比,性别、年龄、身高、体重指数、血糖、血尿素氮、血肌酐、血尿酸、高血压家族史阳性率有统计学差异(P<0.05)。按不同基因型分组后,AA型、AG型、GG型三组比较,年龄、体重指数、收缩压、舒张压、总胆固醇、甘油三酯、高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)、血糖、血尿素氮、血肌酐、血尿酸无统计学差异(P>0.05)。(3)高血压组AA型、AG型、GG型频率分别为49.25%、46.27%、4.48%；对照组分别为55.56%、38.89%、5.55%,两组基因型频率分布无统计学差异(P>0.05)。同时,高血压组A等位基因频率为72.4%,G等位基因频率为27.6%,对照组分别为75.0%和25.0%,两组等位基因频率分布也无统计学差异(P>0.05)。(4)多元逐步回归分析发现,收缩压的独立影响因素包括：年龄(P<0.0001)、体重指数(P=0.0014)、高密度脂蛋白胆固醇(P=0.0974)；舒张压的独立影响因素是：体重指数(P<0.0001)、血肌酐(P=0.0107)、总胆固醇(P=0.1103)；而脉压的独立影响因素为：年龄(P<0.0001)、基因型(P=0.1299)、体重指数(P=0.0864)、高密度脂蛋白胆固醇(P=0.0654)。多元逐步回归分析进入和剔除标准均为0.15。(5)调整年龄、性别、体重指数和降压治疗后,AA型、AG型和GG型三种基因型之间收缩压、舒张压及脉压差别无统计学意义(P>0.05)。在调整年龄、性别、体重指数和降压治疗,同时合并AG型与GG型后,G等位基因携带者和AA型之间收缩压、舒张压及脉压差别也无统计学意义(P>0.05)。[结论](1)大理白族高血压患者AA型、AG型、GG型频率分别为49.25%、46.27%、4.48%,A等位基因频率和G等位基因频率分别为72.4%和27.6%；健康人员AA型、AG型、GG型频率为55.56%、38.89%、5.55%,A等位基因频率和G等位基因频率分别为75.0%和25.0%。(2)AGT基因A-6G多态性与白族人群原发性高血压无关,可能对白族人群原发性高血压的发病影响不大。(3)年龄、体重指数、高密度脂蛋白胆固醇是收缩压的独立影响因素；体重指数、血肌酐、总胆固醇是舒张压的独立影响因素；年龄、基因型、体重指数、高密度脂蛋白胆固醇是脉压的独立影响因素。更多还原

【Abstract】 Objective:To evaluate the relationship between the A-6G polymorphism of the promoter region of angiotensinogen (AGT) gene and essential hypertension in Bai nation of Dali.Methods:The study is consisting of 67 hypertensive subjects (hypertensive group) and 54 normotensive controls (control group) from Dali district, and all subjects are Bai nation. The DNA is extracted from anticoagulant of peripheral vein, and the A-6G polymorphism is determined in by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). And some samples are chosen randomly for validating genotype by double-way sequencing fluorescence. The relationship between A-6G polymorphism of the promoter region of AGT gene and essential hypertension of the Bai nation are analyzed by SAS 9.13.Results:(1) There is a nucleotide substitution of promoter region of the AGT gene in the Bai nation. The nucleotide substitution is A-→G at -6 locus.(2) There is significant difference in sex, age, body height, body mass index, fasting blood glucose, serum urea nitrogen, creatinine, uric acid, and the family history of hypertension between hypertensive group and control group (P<0.05). However, there is no significant difference in age, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), fasting blood glucose, serum urea nitrogen, creatinine, and uric acid between AA, AG and GG genotypes (P>0.05).(3) The frequencies of AA, AG and GG in hypertensive group is 49.25%,46.27%, 4.48% respectively, and is 55.56%,38.89%,5.55% in control group. There is no significant difference in the distribution of genotype frequency between hypertensive group and control group (P>0.05). Meanwhile, the frequencies of A allele is 72.4% and G allele is 27.6% in hypertensive group, and in control group, the frequencies of A allele is 75.0% and G allele is 25.0%, there is also no significant difference in the distribution of frequencies of allele (P>0.05).(4) According to the result of multiple regression analysis (a=0.15), the determinants of systolic blood pressure are age (P<0.0001), body mass index (P=0.0014), high density lipoprotein cholesterol (HDL-C) (P=0.0974); the determinants of diastolic blood pressure are body mass index (P<0.0001), creatinine (P=0.0107), total cholesterol (P=0.1103); And the determinants of pulse pressure are age (P<0.0001), genotype (P=0.1299), body mass index (P=0.0864), high density lipoprotein cholesterol (HDL-C) (P=0.0654).(5) Before and after adjustment of age, sex, body mass index and antihypertensive treatment, there is no significant difference of systolic blood pressure, diastolic blood pressure, pulse pressure between three genotypes of AGT A-6G polymorphism (P> 0.05). Before and after adjustment of age, sex, body mass index and antihypertensive treatment, there is no significant difference of systolic blood pressure, diastolic blood pressure, pulse pressure between AA homozygote and G allele carrier (P>0.05).Conclusion:(1) In the Bai nation population, the frequencies of AA, AG and GG in hypertensive is 49.25%,46.27%,4.48% respectively, and the frequencies of A allele is 72.4% and G allele is 27.6%. However, the frequencies of AA, AG and GG in the healthy is 55.56%,38.89%,5.55% respectively and the frequencies of A allele is 75.0% and G allele is 25.0%.(2) There is no significant correlation between A-6G polymorphism of the promoter region of AGT gene and essential hypertension in the Bai nation, which suggests that the A-6G polymorphism of AGT may be is not involved in the pathogenesis of essential hypertension in the Bai nation.(2) The independent determinants of systolic blood pressure are age, body mass index and high density lipoprotein cholesterol (HDL-C); the independent determinants of diastolic blood pressure are body mass index, creatinine and total cholesterol; and the independent determinants of pulse pressure are age, genotype, body mass index and high density lipoprotein cholesterol (HDL-C).更多还原