青岛地区汉族老年人群AGT基因M235T基因多态性与老年高血压病及靶器官损害的相关性研究

发布时间：2018-05-08 19:23

本文选题：AGTM235T + 单核苷酸多态性　；参考：《青岛大学》2015年博士论文

【摘要】：目的:探讨青岛地区汉族老年人群血管紧张素原(angiotensinogen,AGT)基因M235T多态性与高血压病及靶器官损害的相关性,尽早判断发生高血压靶器官损害的危险性,为早期筛查、早期预治和基因芯片的开发等提供重要依据。方法:利用MS-PCR法扩增检测394例老年高血压患者及186例老年人正常血压者AGT基因M235T的基因型,分别收集一般资料、检测血生化指标及心脏、颈动脉超声,检查脑CT或核磁共振,同时分别按照靶器官损害诊断标准分为高血压病并肾损害、心肌肥厚及动脉硬化、脑梗塞4组,并对各组间基因型频率、等位基因频率及临床指标相关性进行分析。结果:(1)AGT基因M235T共检出TT、MT、MM3种基因型,符合Hardy-Weinberg平衡定律,TT、MT、MM基因型频率为0.531、0.391、0.078,T等位基因频率为0.727,M等位基因频率为0.273。老年高血压病组及对照组比较基因型频率及等位基因频率有统计学差异(p0.05)。(2)单纯EH组基因频率与对照组相比无统计学差异(p0.05),T等位基因频率高于对照组,有统计学差异(p0.05),与合并靶器官损害组相比,基因型频率无统计学差异(p0.05)。(3)左室肥厚组TT型基因频率及T等位基因频率明显高于EH组,有统计学差异(p0.05),肾损害组、动脉硬化组、脑梗塞组与单纯EH组比较基因型频率及等位基因频率差异无统计学意义(p0.05)。(4)老年高血压组中TT组收缩压及舒张压明显高于MT组及MM组,差异有统计学意义(p=0.000),余指标三组无统计学差异(p0.05)。(5)Logistic回归分析表明,AGT基因M235T(TT型)、男性、吸烟、超敏C反应蛋白为老年性高血压发生的危险性因素,AGT基因M235T(TT型)、年龄为老年高血压肾损害的危险性因素;吸烟、LDL-C、hs CRP、SBP为老年高血压合并动脉硬化的危险性因素,HDL-C为老年高血压合并动脉硬化的保护性因素;M235T(TT型)与老年性高血压合并动脉硬化无相关性;年龄、M235T(TT型)为老年高血压合并左室肥厚的危险性因素,;LDL-C、SBP、M235T(TT型)、吸烟为老年高血压合并脑梗塞的危险性因素,而HDL-C为老年高血压合并脑梗塞的保护性因素。结论:(1)1.AGT基因M235T在青岛地区汉族老年人群中存在(TT、MT、MM型)三种位点突变表型。(2)首次证明AGT基因TT型位点突变为青岛地区老年汉族人群发生高血压病危险性因素。(3)3.AGT基因TT型位点突变是青岛地区老年汉族高血压病人群发生肾损害、左室肥厚及脑梗塞的危险因素。
[Abstract]:Objective: To investigate the correlation of angiotensinogen (AGT) gene M235T polymorphism with hypertension and target organ damage in the elderly population of Qingdao Han population, and to determine the risk of target organ damage in hypertension as early as possible and provide important basis for early screening, early pre treatment and gene chip development. Methods: using MS-PCR method. The genotypes of the AGT gene M235T in 394 elderly hypertensive patients and 186 aged people with normal blood pressure were detected, and the general data were collected, the blood biochemical indexes and the heart and carotid ultrasound were detected. The brain CT or MRI were examined. At the same time, the diagnostic criteria of target organ damage were divided into hypertension and renal damage, myocardial hypertrophy and arteriosclerosis. The results were as follows: (1) AGT gene M235T detected TT, MT, MM3 genotypes, TT, MT, MM genotype frequency of 0.531,0.391,0.078, T allele frequency 0.727, M allele frequency was old age. There was significant difference in genotype frequency and allele frequency (P0.05) in the hypertensive group and the control group (P0.05). (2) there was no statistical difference between the EH group and the control group (P0.05), and the frequency of T allele was higher than that of the control group (P0.05), and there was no statistical difference between the genotype frequency and the target organ damage group (P0.05). (3) the frequency of TT gene and T allele in the left ventricular hypertrophy group were significantly higher than that in the EH group, and there was a statistically significant difference (P0.05). There was no significant difference in the genotype frequencies and allele frequencies of the renal damage group, the arteriosclerosis group, the cerebral infarction group and the EH group (P0.05). (4) the systolic pressure and diastolic pressure of the TT group in the elderly hypertensive group were significantly higher than that of the MT group. And MM group, the difference was statistically significant (p=0.000), and there was no statistical difference between the three groups (P0.05). (5) Logistic regression analysis showed that the AGT gene M235T (TT type), male, smoking, and hypersensitive C reactive protein were risk factors for the occurrence of senile hypertension, AGT gene M235T (TT type), age as risk factors for elderly hypertensive renal damage; smoking, LDL. -C, HS CRP, SBP are the risk factors for elderly hypertension with arteriosclerosis. HDL-C is a protective factor for elderly hypertension with arteriosclerosis; M235T (TT) is not associated with senile hypertension with arteriosclerosis; age, M235T (TT type) is a risk factor for elderly hypertension with left ventricular hypertrophy, LDL-C, SBP, M235T (type), smoking as a factor. The risk factors of senile hypertension combined with cerebral infarction, and HDL-C as protective factors for senile hypertension combined with cerebral infarction. Conclusion: (1) the 1.AGT gene M235T has three loci mutation phenotypes (TT, MT, MM) in the elderly population of Qingdao region. (2) it is the first time that the mutation of the AGT gene TT type loci is higher in the elderly Han population in Qingdao region. The risk factors of blood pressure disease. (3) 3.AGT gene TT mutation is a risk factor for renal damage, left ventricular hypertrophy and cerebral infarction in elderly Han people with hypertension in Qingdao.

【学位授予单位】：青岛大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R544.1

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