[Insulin receptor gene in an etiology of Japanese NIDDM]

We reviewed 23 Japanese patients with mutation in the insulin receptor gene. In general, patients with two mutant alleles tend to be more severely insulin-resistant than those with one mutant allele. Most of the mutations have been identified in patients with genetic syndromes associated with extreme insulin resistance. However, some patients having a mutation in the insulin receptor gene (especially in the tyrosine kinase domain), were moderately insulin-resistant. In these cases, despite having a same mutation in the insulin receptor gene, some individuals exhibited significant clinical differences (e.g. insulin resistance or glucose tolerance). Although mutations in the insulin receptor gene can cause insulin resistance, we assume that other genetic or behavioral factors may alter the clinical phenotype in patients with same mutations in the insulin receptor gene. Nevertheless, mutations in the insulin receptor gene may be a contributory cause of insulin resistance in a subpopulation (approximately 1%) of NIDDM.