Clinical utility of HNF1A genotyping for diabetes in aboriginal Canadians.
OBJECTIVE
To determine the diagnostic performance characteristics of HNF1A genotyping for diabetes and impaired glucose tolerance (IGT) in Canadian Oji-Cree Indians.


METHODS
We studied all Oji-Cree subjects > or = 50 years of age (96 subjects) who had participated in a community-wide prevalence survey for type 2 diabetes. Subjects were classified either as having "disease," which included type 2 diabetes and IGT, or not. All 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, sensitivity, 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 probability of disease after a negative test was 42.2%. The values were very similar for the subgroup of subjects with type 2 diabetes alone.


CONCLUSIONS
The HNF1A genotype appears to be the most specific genetic test yet reported for the prediction of a common multifactorial disease by applying 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 HNF1A S319 had a reduced risk compared with the age-specific prevalence but was not totally risk-free. Because HNF1A S319 was not the only predisposing factor for diabetes in the Oji-Cree, subjects without HNF1A S319 were still at some risk for diabetes or IGT.
Hegele
R A
RA
John P. Robarts Research Institute, and Department of Medicine, University of Western Ontario, London, Canada. robert.hegele@rri.on.ca
Cao
H
H
Hanley
A J
AJ
Zinman
B
B
Harris
S B
SB
Anderson
C M
CM
D002170:Canada / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004268:DNA-Binding Proteins; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D018149:Glucose Intolerance / Q000453:epidemiology / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D015995:Prevalence; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta