Caulfield M, Lavender P, Newell-Price J, Farrall M, Kamdar S, Daniel H, Lawson M, De Freitas P, Fogarty P, Clark A J
Department of Clinical Pharmacology, St. Bartholomew's Hospital, London, United Kingdom.
J Clin Invest. 1995 Aug;96(2):687-92. doi: 10.1172/JCI118111.
The renin-angiotensin system regulates blood pressure and sodium balance. The angiotensinogen gene which encodes the key substrate within this system has been linked to essential hypertension in White Europeans. It has been suggested that people of West African ancestry may have a different genetic basis for hypertension. In this study we have tested whether there is linkage of the angiotensinogen gene to essential hypertension in African Caribbeans from St. Vincent and the Grenadines. DNA from 63 affected sibling pairs with hypertension was tested for linkage by analyzing whether there was excess allele sharing among siblings genotyped using an angiotensinogen dinucleotide repeat sequence. There was significant support for linkage (T = 3.07, P = 0.001) and association of this locus to hypertension (chi 2 = 50.2, 12 degrees of freedom, P << 0.001). A DNA polymorphism which alters methionine to threonine at position 235 (M235T) within the angiotensinogen peptide has been associated previously with hypertension. However, we found no association of this variant with hypertension in this study. These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity.
肾素-血管紧张素系统调节血压和钠平衡。编码该系统关键底物的血管紧张素原基因已与欧洲白人的原发性高血压相关联。有人提出,西非血统的人可能有不同的高血压遗传基础。在本研究中,我们测试了血管紧张素原基因与来自圣文森特和格林纳丁斯的非洲加勒比人中的原发性高血压是否存在连锁关系。通过分析使用血管紧张素原二核苷酸重复序列进行基因分型的同胞之间是否存在等位基因共享过多,对63对患有高血压的患病同胞对的DNA进行了连锁测试。有显著证据支持该位点与高血压的连锁关系(T = 3.07,P = 0.001)以及该位点与高血压的关联(卡方 = 50.2,自由度为12,P << 0.001)。血管紧张素原肽中第235位的甲硫氨酸变为苏氨酸的DNA多态性(M235T)先前已与高血压相关联。然而,在本研究中我们未发现该变体与高血压有关联。这些发现为血管紧张素原位点与非洲加勒比人中的高血压的连锁关系和关联提供了证据,并表明不同种族人群原发性高血压的遗传基础存在一些相似之处。