Mining the genome for susceptibility to diabetic nephropathy: the role of large-scale studies and consortia

Semin Nephrol. 2007 Mar;27(2):208-22. doi: 10.1016/j.semnephrol.2007.01.004.

Abstract

Approximately 30% of individuals with type 1 and type 2 diabetes develop persistent albuminuria, lose renal function, and are at increased risk for cardiovascular and other microvascular complications. Diabetes and kidney diseases rank within the top 10 causes of death in Westernized countries and cause significant morbidity. Given these observations, genetic, genomic, and proteomic investigations have been initiated to better define basic mechanisms for disease initiation and progression, to identify individuals at risk for diabetic complications, and to develop more efficacious therapies. In this review we have focused on linkage analyses of candidate genes or chromosomal regions, or coarse genome-wide scans, which have mapped either categorical (chronic kidney disease or end-stage renal disease) or quantitative kidney traits (albuminuria/proteinuria or glomerular filtration rate). Most loci identified to date have not been replicated, however, several linked chromosomal regions are concordant between independent samples, suggesting the presence of a diabetic nephropathy gene. Two genes, carnosinase (CNDP1) on 18q, and engulfment and cell motility 1 (ELMO1) on 7p14, have been identified as diabetic nephropathy susceptibility genes, but these results require authentication. The availability of patient data sets with large sample sizes, improvements in informatics, genotyping technology, and statistical methodologies should accelerate the discovery of valid diabetic nephropathy susceptibility genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Diabetic Nephropathies / genetics*
  • Dipeptidases / genetics*
  • Genetic Linkage*
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Humans
  • Ligands
  • Prognosis

Substances

  • Adaptor Proteins, Signal Transducing
  • ELMO1 protein, human
  • Ligands
  • Dipeptidases
  • aminoacyl-histidine dipeptidase