MOLECULAR STUDIES OF THE GENETICS OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Non-insulin-dependent mellitus (NIDDM) is a common, multi-factorial di sease with a significant genetic component to disease susceptibility. Biometrical analysis of family data has consistently found evidence of the action of a major gene in determining susceptibility to NIDDM in families. However, the identity of the gene or genes that contribute t o NIDDM in the general population is still not known. Recent advances in molecular biology have given investigators access to a number of pl ausible candidate genes for NIDDM and these have been used as test loc i in association and linkage studies with inconsistent results. A revi ew of the candidate gene studies in NIDDM suggests that the failure of these studies to identify specific loci involved in conferring suscep tibility to NIDDM is, in part, due to failure to incorporate a number of biological features of the disease. The frequency of NIDDM in the p opulation suggests that the alleles involved in NIDDM are common and t heir individual impact too small to be detected by simple single locus methods of analysis. Studies of other phenotypic forms of diabetes me llitus suggest that susceptibility to NIDDM is probably determined by alleles at more than one locus acting independently or in concert. The evolutionary history of certain populations may have isolated alleles conferring susceptibility to NIDDM in ethnically defined populations at high risk of NIDDM. These populations may provide a unique opportun ity to identify specific genes involved in the complex etiology of NID DM. (C) 1993 Wiley-Liss, Inc.