Hegele R A, Cao H, Hanley A J, Zinman B, Harris S B, Anderson C M
John P. Robarts Research Institute, and Department of Medicine, University of Western Ontario, London, Canada.
Diabetes Care. 2000 Jun;23(6):775-8. doi: 10.2337/diacare.23.6.775.
To determine the diagnostic performance characteristics of HNF1A genotyping for diabetes and impaired glucose tolerance (IGT) in Canadian Oji-Cree Indians.
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.
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.
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.
确定HNF1A基因分型对加拿大奥吉 - 克里印第安人糖尿病和糖耐量受损（IGT）的诊断性能特征。
我们研究了所有年龄≥50岁的奥吉 - 克里受试者（96名），他们参与了社区范围内的2型糖尿病患病率调查。受试者被分类为患有“疾病”（包括2型糖尿病和IGT）或未患“疾病”。所有受试者均进行了HNF1A G319S突变的基因分型。
该组疾病患病率为65.7%，其中71.4%患有2型糖尿病。对于HNF1A S319携带者，特异性、敏感性、阳性和阴性预测值分别为97.0%、30.1%、95.0%和42.1%。当考虑检测前疾病患病率时，检测阳性后患病的概率为97.2%，检测阴性后患病的概率为42.2%。仅患有2型糖尿病的受试者亚组的结果非常相似。
根据分子遗传学中临床流行病学的现行标准，HNF1A基因型似乎是迄今为止报道的用于预测常见多因素疾病的最具特异性的基因检测。检测阳性结果在奥吉 - 克里人中具有特殊诊断价值：携带HNF1A S319的受试者在50岁时几乎肯定患有糖尿病或IGT。相比之下，未携带HNF1A S319的受试者与特定年龄患病率相比风险降低，但并非完全无风险。由于HNF1A S319不是奥吉 - 克里人中糖尿病的唯一易感因素，未携带HNF1A S319的受试者仍有患糖尿病或IGT的一定风险。
