Liu Y, Qiu C, Zhou W, Zheng Y, Hou S, Cao J
Department of Pathological Biochemistry, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, Tottori 683, Japan.
Chin Med J (Engl). 1999 Feb;112(2):115-20.
To determine whether angiotensin-converting enzyme (ACE) gene, angiotensinogen (AGT) gene and angiotensin II receptor 1 (AT1R) gene are implicated in Chinese essential hypertension (EH).
The case-control and haplotype-based haplotype relative risk (HHRR) study consisted of 169 essential hypertensive subjects (HT), 152 normotensive controls (NT) and 62 families. The polymorphisms of insertion/deletion (I/D) allele of ACE gene and the microsatellite allele of AT1R gene were determined in DNA extracted from peripheral blood leukocytes by polymerase chain reaction (PCR). The variants of AGT gene were screened by PCR-single strand conformation polymorphism (PCR-SSCP) analysis and further identified by cloning and sequencing.
The significant association between EH and D allele of ACE gene was found (P < 0.05). The difference of the microsatellite allele distribution of AT1R gene between HT and NT groups was statistically significant (P < 0.005). By contrast, the distribution of A-20C genotype of AGT gene was almost identical in HT and NT groups. No significant linkage disequilibrium was observed between A-20C and M235T in AGT gene.
D allele of ACE gene might correlate with a predisposing factor for EH. The microsatellite allele of AT1R gene might be linkage disequilibrium with an unidentified variant that contributes to the development of EH. A-20C of AGT gene is not a major genetic determinant of EH.
确定血管紧张素转换酶(ACE)基因、血管紧张素原(AGT)基因和血管紧张素II受体1(AT1R)基因是否与中国原发性高血压(EH)有关。
病例对照和基于单倍型的单倍型相对风险(HHRR)研究包括169例原发性高血压患者(HT)、152例血压正常对照者(NT)和62个家庭。采用聚合酶链反应(PCR)从外周血白细胞提取的DNA中检测ACE基因插入/缺失(I/D)等位基因多态性和AT1R基因微卫星等位基因。通过PCR-单链构象多态性(PCR-SSCP)分析筛选AGT基因变异,并通过克隆和测序进一步鉴定。
发现EH与ACE基因的D等位基因之间存在显著关联(P<0.05)。HT组和NT组之间AT1R基因微卫星等位基因分布差异具有统计学意义(P<0.005)。相比之下,HT组和NT组AGT基因A-20C基因型的分布几乎相同。在AGT基因中,未观察到A-20C与M235T之间存在显著连锁不平衡。
ACE基因的D等位基因可能与EH的易感因素相关。AT1R基因的微卫星等位基因可能与一个未确定的变异存在连锁不平衡,该变异促成了EH 的发生发展。AGT基因的A-20C不是EH的主要遗传决定因素。