Brown D M, Provoost A P, Daly M J, Lander E S, Jacob H J
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Nat Genet. 1996 Jan;12(1):44-51. doi: 10.1038/ng0196-44.
Hypertension, diabetes and hyperlipidemia are risk factors for life-threatening complications such as end-stage renal disease, coronary artery disease and stroke. Why some patients develop complications is unclear, but only susceptibility genes may be involved. To test this notion, we studied crosses involving the fawn-hooded rat, an animal model of hypertension that develops chronic renal failure. Here, we report the localization of two genes, Rf-1 and Rf-2, responsible for about half of the genetic variation in key indices of renal impairment. In addition, we localize a gene, Bpfh-1, responsible for about 26% of the genetic variation in blood pressure. Rf-1 strongly affects the risk of renal impairment, but has no significant effect on blood pressure. Our results show that susceptibility to a complication of hypertension is under at least partially independent genetic control from susceptibility to hypertension itself.
高血压、糖尿病和高脂血症是诸如终末期肾病、冠状动脉疾病和中风等危及生命并发症的风险因素。为何有些患者会出现并发症尚不清楚,但可能仅涉及易感基因。为验证这一观点,我们研究了涉及小鹿帽鼠的杂交实验,小鹿帽鼠是一种会发展为慢性肾衰竭的高血压动物模型。在此,我们报告了两个基因Rf-1和Rf-2的定位,这两个基因负责约一半的肾功能损害关键指标的遗传变异。此外,我们定位了一个基因Bpfh-1,它负责约26%的血压遗传变异。Rf-1强烈影响肾功能损害风险,但对血压无显著影响。我们的结果表明,高血压并发症的易感性至少部分受独立于高血压本身易感性的遗传控制。