Diabetes Mellitua as An Inheritable Disease : Recent Results Obtained by Molecular Genetics (Recent Advances in Research and Treatment of Diabetes Mellitus)

Although non-insulin-dependent diabetes mellitus (NIDDM) has been widely thought to be an inheritable disease, the identification of a major gene in NIDDM has not been demonstrated by the classical genetics. One of reasons for the failure to find any clear trend was due to the fact that NDDM is a multifactorial disease, in which several major genes are involved in the onset and progression. This fact was partly demonstrated from monozygotic twin studies. However, we now can have a cue to identify the major genes of NIDDM by virtue of molecular biology (recombinant DNA technology). There are at least three major approach to identify a disease susceptibility gene ; classical approach, reverse genetics (positional cloning) and candidate gene approach. Mutations in insulin gene in patients with abnormal insulinemia were identified by classical approach, in which abnormal insulin was firstly isolated from patients' blood, and secondly, the gene coding the abnormal insulin was isolated by molecular cloning. Positional cloning is a method to identify a disease susceptibility gene based on the linkage analysis between various well-known genetic markers and the disease. By this method, it has been demonstrated that gene for maturity-onset diabetes of the young (MODY), a from of NIDDM with an autosomal dominant inheritance is linked to adenosine deaminase gene locus on chromosome 20q. Candidate gene approach is the method to examine whether the genes which are thought to be involved in the abnormal phenotype of a disease, is related to the disease or not. In 1992, close linkage of glucokinase gene locus on chromosome 7p to MODY of French families has been revealed, and furthermore, non-sense mutation in the glucokinase gene has been identified in one of the families. Although the tremedous progress in molecular biology is of benefit to us to obtain various genetic informations of NIDDM such as described above, the cases in which mutations in genes were identified until now in Japanese patients with NIDDM are quite rare. Therefore, we might have a time identifying all gene abnormalities in all patients with NIDDM