Niu T, Xu X, Rogus J, Zhou Y, Chen C, Yang J, Fang Z, Schmitz C, Zhao J, Rao V S, Lindpaintner K
Program for Population Genetics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
J Clin Invest. 1998 Jan 1;101(1):188-94. doi: 10.1172/JCI119876.
The renin-angiotensin system plays a major role in regulating blood pressure and maintaining electrolyte and volume homeostasis. Previously, the angiotensinogen gene, which encodes the key substrate for renin within this system, has been reported linked to and associated with essential hypertension in White Europeans, African-Caribbeans, and Japanese. Therefore, we investigated whether the angiotensinogen gene might be similarly implicated in the pathogenesis of essential hypertension in Chinese by carrying out linkage analysis in 310 hypertensive sibling pairs. Genotypes for two diallelic DNA polymorphisms observed at amino acid residues 174 (T174M) and 235 (M235T) within the coding sequence and for two highly informative dinucleotide (GT)-repeat sequences (one in the 3' flanking region, and one at a distance of 6.1 cM from the gene) were determined. Affected sibpair analysis conducted according to three different algorithms (S.A.G.E./SIBPAL, MAPMAKER/ SIBS, and APM methods) revealed no evidence for linkage of the angiotensinogen gene to hypertension. Our data indicate that molecular variants of this gene do not appear to contribute materially to the pathogenesis of primary hypertension among Chinese (a notion supported by concomitant, direct estimates of power), and that the disease relevance of this gene may vary therefore depending on ethnicity.
肾素 - 血管紧张素系统在调节血压以及维持电解质和容量稳态方面发挥着主要作用。此前,有报道称血管紧张素原基因(该系统中肾素的关键底物编码基因)与欧洲白人、非洲加勒比人和日本人的原发性高血压有关联。因此,我们通过对310对高血压同胞对进行连锁分析,研究血管紧张素原基因在中国原发性高血压发病机制中是否也有类似作用。测定了编码序列中氨基酸残基174(T174M)和235(M235T)处观察到的两个双等位基因DNA多态性以及两个信息丰富的二核苷酸(GT)重复序列(一个在3'侧翼区域,另一个距该基因6.1厘摩)的基因型。根据三种不同算法(S.A.G.E./SIBPAL、MAPMAKER/SIBS和APM方法)进行的患病同胞对分析未发现血管紧张素原基因与高血压连锁的证据。我们的数据表明,该基因的分子变异在中国原发性高血压发病机制中似乎没有实质性作用(同时进行的直接效能估计也支持这一观点),因此该基因与疾病的相关性可能因种族而异。