HEPATOCYTE NUCLEAR FACTOR-1-ALPHA GENE AND NON-INSULIN-DEPENDENT DIABETES-MELLITUS IN THE JAPANESE POPULATION

Recently, hepatocyte nuclear factor-1 alpha (HNF-1 alpha which is enco ded by the TCF1 gene) mutations were reported in a subset of patients with maturity onset diabetes of the young (MODY3). We studied the cont ribution of TCF1 to genetic susceptibility to common non-insulin-depen dent diabetes mellitus (type 2) in Japanese subjects by investigating allelic association with type 2 diabetes use of three markers. We also studied the frequency of the G191D mutation, the only mutation of TCF 1 reported so far in late-onset type 2 diabetes. A total of 356 subjec ts were studied. There were no significant differences in allele frequ ency of the three markers between patients with type 2 diabetes and co ntrol subjects. A G191D mutation was not found in the subjects studied , giving a frequency of less than 0.4% in common type 2 diabetes. The lack of association of type 2 diabetes with three markers in and near TCF1 suggests that mutations in TCF1 derived from a limited number of founders are not a major cause of common type 2 diabetes even in the g enetically homogeneous Japanese population. The data also indicate tha t the G191D mutation in TCF1 plays little, if any, role in susceptibil ity to common type 2 diabetes in the Japanese.