摘要
目的：血管紧张素Ⅱ1型受体(AT1R)是血压调节过程中的重要因素，并与高血压靶器官损害有关。AT1R基因的差异造成AT1R的功能改变。本课题旨在研究AT1R基因1166A/C单核苷酸多态性在中国南方汉族人群的分布特征及其与高血压病及其左室重构的关联关系，以期从分子水平探讨高血压发病和预后的机制及特点，为高血压病及其重要靶器官损伤遗传易感基因的识别和高血压病的防治提供科学依据。
方法：采用病例对照研究，结合聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术，检测148例高血压病患者和164例对照者的AT1R基因1166位点基因型和等位基因，比较和分析病例组与对照间该基因型及等位基因的分布频率差异，并按胆固醇水平和年龄分层，分析遗传因素对发病的影响特点；分析该遗传因素对高血压患者左室重构的作用，并运用Logistic回归分析基因型对高血压病及左室重构的独立危险性。
结果：312例样本中发现AT1R基因1166位点全部3种基因型；C等位基因在病例组和对照组中频率分别为0.111和0.055，P＜0.05；按血清胆固醇水平分层后，C等位基因在均为高胆固醇的病例与对照组中的频率分别为0.144和0.046，P＜0.01；按起病年龄分层后，C等位基因在病例组青年和对照组青年中频率分别为0.182和0.054，P＜0.01；用协方差剔除其他混杂因素后，病例组内AA型和AC/CC型左室重量指数均数分别116.08和127.23，P＜0.05；Logistic回归分析后，AC/CC基因型对高血压病和高血压左室重构的OR分别为1.998(95％CI：1.073～3.851)和2.482(95％CI：1.203～9.796)。
结论：AT1R基因1166A/C单核苷酸多态性与高血压病的发生有关联关系，C等位基因是该病的易患基因，AC/CC基因型为易患基因型；该等位基因尚参与高血压病的早发，并增加高胆固醇血症者的患病危险；该等位基因与高血压左室重构有关，是该变化的易患基因。
Objective Angiotensin II type 1 receptor (AT1R) is one of the important factors in the process of blood pressure regulation, as well as in the damage of target organs. The mutations of ATIR gene lead to the changes of ATIR function. The current study was conduct to analyze the distribution characters of single nucleotide polymorphisms 1166A/C of AT1R gene (SNP), and to investigate the association between AT1R gene SNP and essential hypertension and hypertensive left ventricular remodeling in Chinese Southern Hans. The research was expected to provide the basis of identification of predisposing genes and prevention and cure for essential hypertension.
Methods A case-control study of 148 cases and 164 controls was carried out with molecular epidemiological study and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The AT1R genotype and gene frequencies were analyzed, and further hierarchical analyses were conducted according age and serum total cholesterol (TC). Independent fatalness of AT1R genotypes and alleles toward hypertension and hypertensive left ventricular remodeling were analyzed by Logistic regression.
Results All the 3 genotypes in site 1166 of ATI R gene were identified among 312 individuals. The 1166C allele frequency of AT1R gene was 0.111 in cases and 0.055 in controls (P<0.05); in all subjects with hypercholesterolemia when serum TC level was hierarchically analyzed, the 1166C allele frequency in two groups was 0.144 and 0.046 respectively (PO.01); in youth of cases and controls, the frequency was 0.182 and 0.054 respectively (P<0.01). Hypertensives with AC/CC genotypes had more increased LVMI than those with AA genotype when covariant factors were rejected (127.23 : 116.08, P<0.05). The 1166C allele was related with hypertension and hypertensive left ventricular remodeling when analyzed by Logistic regression, the OR is 1.998 (95%CI: 1.073-3.851) and2.482 (95%CI: 1.203-9.796) respectively.
Conclusion 1166A/C SNP is associated with hypertension development. 1166C is susceptible allele and 1166AC/CC are susceptible genotypes. Further more, 1166C allele
is concerned with the development of premature essential hypertension and can increase the fatalness of suffering from hypertension in subjects with hypercholesterolemia. And 1166C is susceptible allele for the development of hypertensive left ventricular remodeling.
引文
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