Genetics of diabetic complications

Abstract

In 1965 Neel described diabetes mellitus as the “geneticist's nightmare”. 1 Neel JV Diabetes mellitus. in: Neel JV Shaw MW Schull WJ The genetics and epidemiology of chronic disease. US Public Health Service Publications, Washington1965: 105-132 Google Scholar Twin, family, and transracial studies suggested that inherited factors were important in the aetiology of the disease. It is now recognised that multiple genes, interacting with the environment, contribute to disease susceptibility. Despite the complexity of the picture, it has been possible to reduce the nightmare into just a “bad dream” by concentrating on specific subgroups of type 1 and type 2 diabetes. Thus in recent years the genes responsible for some cases of maturity-onset diabetes of the young (MODY), 2 Horikawa Y Iwasaki N Hara M et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet. 1997; 17: 384-385 Crossref PubMed Scopus (730) Google Scholar , 3 Yamagata K Furuta H Oda N et al. Mutations in the hepatocyte nuclear factor-4 alpha gene in maturity-onset diabetes of the young. Nature. 1996; 384: 458-460 Crossref PubMed Scopus (1035) Google Scholar , 4 Vionnet N Stoffel M Takeda J et al. Nonsense mutation in the glucokinase gene causes early-onset non-insulin dependent diabetes mellitus. Nature. 1992; 356: 721-722 Crossref PubMed Scopus (552) Google Scholar maternally inherited diabetes, 5 Alcolado JC Thomas AW Maternally inherited diabetes mellitus: the role of mitochondrial DNA defects. Diabet Med. 1995; 12: 102-108 Crossref PubMed Scopus (40) Google Scholar and severe insulin resistance 6 Baynes KC Whitehead J Krook A O'Rahilly S Molecular mechanisms of inherited insulin resistance. Q J Med. 1997; 90: 557-562 Crossref Scopus (14) Google Scholar have been identified and several genome-wide searches have suggested possible loci for the more common forms of type 2 diabetes. 7 Hanis CL Boerwinkle E Chakraborty R et al. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat Genet. 1996; 13: 161-166 Crossref PubMed Scopus (554) Google Scholar The genetic basis of type 1 diabetes has also come under close scrutiny, with several gene loci, including the HLA and insulin gene regions, being implicated in many populations. 8 Todd JA Farrall M Panning for gold: genome-wide scanning for linkage in type 1 diabetes. Hum Molec Genet. 1996; 5: 1443-1448 PubMed Google Scholar