Clinical utility of HNF1A genotyping for diabetes in Aboriginal Canadians

OBJECTIVE - To determine the diagnostic performance characteristics of HNF1 A genotyping for diabetes and impaired glucose tolerance (IGT) in Canadian Oji-Cree Indians. RESEARCH DESIGN AND METHODS - We studied all Oji-Cree subjects greater than or equal to 50 years of age (96 subjects) who had participated in a commun ity-wide prevalence survey for type 2 diabetes. Subjects were classified ei ther as having "disease," which included type 2 diabetes and IGT, or not. A ll subjects were genotyped for the HNF1A G319S mutation. RESULTS - The prevalence of disease in this group was 65.7%, of whom 71.4% had type 2 diabetes. For a carrier of HNF1A S319. the specificity, sensitiv ity and positive and negative predictive values were 97.0, 30.1, 95.0, and 42.1%, respectively. When the pretest disease prevalence was accounted for, the probability of disease after a positive test was 97.2%, and the probab ility of disease after a negative test was 42.2%. The values were very simi lar for the subgroup of subjects with type 2 diabetes alone. CONCLUSIONS - The HNF1A genotype appears to be the most specific genetic te st yet reported for the prediction of a common multifactorial disease by ap plying present-day standards of clinical epidemiology in molecular genetics . A positive test result had particular diagnostic value in the Oji-Cree: a subject with HNF1A S319 was virtually certain of having diabetes or IGT by 50 years of age. In contrast, a subject without HNFIA S319 had a reduced r isk compared with the age-specific prevalence but was not totally risk-free . Because HNFIA S319 was not the only predisposing factor for diabetes in t he Oji-Cree, subjects without HNFIA S319 were still at some risk for diabet es or IGT.