Genetics of diabetic nephropathy in the pima indians
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Diabetic nephropathy is the leading cause of renal failure in industrialized countries. There is strong evidence that diabetic nephropathy is influenced by genetic factors. Studies in the Pima Indians as well as in other populations demonstrate that diabetic nephropathy aggregates in families. The hypothesis that the familial aggregation reflects the effect of a major gene was formally tested by segregation analysis of diabetic nephropathy in Pima Indians with type 2 diabetes.
The segregation analysis provided strong evidence for a major genetic effect on the prevalence of diabetic nephropathy; this suggests that some of the genetic determinants of diabetic nephropathy may have effects of sufficient magnitude to be detected by linkage analysis. Therefore, we analyzed data from a genome-wide scan to identify susceptibility loci for nephropathy in diabetic Pima Indians. Analyses conducted by both parametric (model-based) and nonparametric methods revealed tentative evidence for nephropathy susceptibility loci on chromosomes 3q, 7q, 18q, and 20p.
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References and Recommended Reading
- 1.U. S. Renal Data System. 1999 annual data report [no authors listed]. Am J Kidney Dis 1999, 34(2 suppl 1):S9–S19.Google Scholar
- 9.Nelson RG, Knowler WC, Pettitt DJ, et al.: Kidney disease in diabetes. In Diabetes in America, edn 2. Edited by Harris MI. Bethesda, MD: National Institutes of Health; 1995:349–400.Google Scholar
- 30.Knowler WC: Approaches to studying the genetics of type 2 diabetes. In Current Topics in Diabetes Research. Front Diabetes. Edited by Belfiore F et al. Basel, Switzerland: Kanger Press; 1993:1–11.Google Scholar
- 34.Terwilliger JD, Ott J: Parametric analysis of complex diseases. In Handbook of Human Genetic Linkage. Edited by Terwilliger JD, Ott J. Baltimore, MD: The Johns Hopkins University Press; 1994:211–226.Google Scholar
- 35.Hanson RL, Ehm MG, Pettitt DJ, et al.: An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. Am J Hum Genet 1998, 63:1130–1138. Represents a large genomic scan to identify loci influencing susceptibility to diabetes and obesity in the Pima Indians. A diabetessusceptibility locus was identified on chromosome 1q and a diabetesobesity locus on chromosome 11q.PubMedCrossRefGoogle Scholar
- 36.Imperatore G, Hanson RL, Pettitt DJ, et al.: Sib-pair linkage analysis for susceptibility genes for microvascular complications among Pima Indians with type 2 diabetes. Diabetes 1998, 47:821–830. Depicts to our knowledge the first genomic scan to identify diabetic nephropathy susceptibility genes. Tentative evidence for linkage was seen on chromosomes 3q, 7q, and 20p.PubMedCrossRefGoogle Scholar
- 38.Fogarty DG, Moczulski DK, Makita Y, et al.: Evidence for a susceptibility locus for diabetic nephropathy on chromosome 7q in Caucasian families with type 2 diabetes [abstract]. Diabetes 1999, 48(suppl 1):A47.Google Scholar
- 53.Bond JS, Marchand P, Tang J, et al.: Structure and membrane association of mouse and rat meprins. In The Astacins: Structure and Function of a New Protein Family. Edited by Zwilling R, Stocker W. Heidelberg, Germany: Springer-Verlag Publishers; 1997:45–55.Google Scholar