ROLE OF MITOCHONDRIAL-DNA TRANSFER-RNA LEUCINE AND GLUCAGON RECEPTOR MISSENSE MUTATIONS IN UTAH WHITE DIABETIC-PATIENTS

Recently, subtypes of typical NIDDM were suggested based on missense m utations of mitochondrial DNA [tRNA(Leu(UUR))] and the glucagon recept or gene (Gly40Ser). Together these mutations might explain NIDDM in 5- 8% of patients. To test the hypothesis that these mutations play an im portant role in a Northern European population with a strong family hi story of diabetes, we screened members of 45 families selected for hav ing two or more diabetic siblings and 62 additional unrelated diabetic individuals for bath mutations. We also examined 74 nondiabetic contr ol subjects. Mitochondrial DNA mutations were not detected despite our ability to detect as little as 3% heteroplasmy in a sample from an in dividual known to carry the mutation. Likewise, the glucagon receptor Gly40Ser mutation was present in a single diabetic patient who on subs equent investigation was of Italian descent. Thus, neither subtype of NIDDM is present in the Utah diabetic population, which is reflective of other Northern European populations.