Genetic susceptibility to nephropathy in Pima Indians with type 2 diabetesmellitus

In Pima Indians, the incidence of end-stage renal disease, nearly all of wh ich is attributable to type 2 diabetes mellitus, is more than 20 times that in the general United States population. Studies in the Pimas indicate tha t factors other than diabetes per se enhance susceptibility tu the developm ent of diabetic nephropathy. Aggregation of renal disease in families, a re lationship between parental blood pressure and diabetic nephropathy in the offspring, and an association between higher prediabetic blood pressure and the occurrence of renal disease after the onset of diabetes all point to i ndividual differences in susceptibility. Although clustering of environment al exposures may be responsible for these findings, they may also represent genetic transmission of susceptibility to renal disease. Recently, linkage analyses were performed in 98 diabetic sib-pairs, both affected by diabeti c nephropathy. Two adjacent markers on chromosome 7 met the criteria for su ggestive linkage with two-point analysis. Positioned between these markers is the gene coding for aldose reductase. Polymorphisms of this locus are as sociated with diabetic microvascular complications in other populations. Li nkage studies provide evidence that familial aggregation of diabetic renal disease reflects, in part, genetic transmission of susceptibility that appe ars to be independent uf thr transmission of diabetes.