Yu H, Bowden D W, Spray B J, Rich S S, Freedman B I
Department of Biochemistry, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC, USA.
J Am Soc Nephrol. 1996 Dec;7(12):2559-64. doi: 10.1681/ASN.V7122559.
The factors that initiate chronic renal failure in patients with hypertension, diabetes mellitus, and chronic glomerular disease are largely unknown. The likely genetic contribution to ESRD, particularly in African Americans, suggests that linkage analysis may be useful to evaluate the role of candidate genes in the pathogenesis of chronic renal failure. The renin-angiotensin-aldosterone (RAA) axis has been intensively evaluated for its contribution to cardiovascular disease and nephropathy. This study tested for linkage between candidate genes in the RAA axis and chronic renal failure, using 85 African-American sibling pairs (from 65 families) concordant for ESRD. Angiotensinogen was selected because of the putative link between it and mild to moderate essential hypertension and nephrosclerosis; angiotensin-converting enzyme because of its possible contribution to diabetic nephropathy; and renin, the angiotensin II receptor, and kallikrein because of their roles in hypertension and renal perfusion. These candidate loci did not demonstrate linkage to either diabetic or nondiabetic renal disease in this study's collection of sibling pairs. These results suggest that polymorphisms at these RAA axis loci do not make major contributions to the pathogenesis of renal disease in African Americans.
高血压、糖尿病和慢性肾小球疾病患者引发慢性肾衰竭的因素大多未知。对终末期肾病（ESRD）可能的遗传贡献，尤其是在非裔美国人中，表明连锁分析可能有助于评估候选基因在慢性肾衰竭发病机制中的作用。肾素 - 血管紧张素 - 醛固酮（RAA）轴对心血管疾病和肾病的贡献已得到深入评估。本研究使用85对患终末期肾病一致的非裔美国同胞对（来自65个家庭），检测RAA轴中候选基因与慢性肾衰竭之间的连锁关系。选择血管紧张素原是因为它与轻度至中度原发性高血压和肾硬化之间存在假定联系；选择血管紧张素转换酶是因为它可能对糖尿病肾病有影响；选择肾素、血管紧张素II受体和激肽释放酶是因为它们在高血压和肾脏灌注中的作用。在本研究收集的同胞对中，这些候选基因座未显示与糖尿病或非糖尿病肾病存在连锁关系。这些结果表明，这些RAA轴基因座的多态性对非裔美国人肾病的发病机制没有重大贡献。
