Hegele R A
Blackburn Cardiovascular Genetics Laboratory, John P. Robarts Research Institute, 406-100 Perth Drive, London, Ontario, N6A 5K8, Canada.
Curr Atheroscler Rep. 2001 May;3(3):216-21. doi: 10.1007/s11883-001-0064-1.
The incidence of coronary heart disease (CHD) among aboriginal people in northern Ontario has tripled over the past 20 years. This is inextricably linked to the remarkably high prevalence of type 2 diabetes in these native communities. Approximately 40% of the Oji-Cree of northern Ontario have typical obesity-related type 2 diabetes, which represents a drastic increase from virtually unreportable levels 50 years ago. The Oji-Cree have a private mutation in the HNF1A gene, namely G319S, which is absent from other ethnic groups and aboriginal populations. The most compelling reasons that HNF1A S319 is a diabetes-susceptibility allele are its consistent statistical association with the presence and severity of diabetes. Also, HNF1A S319 has specificity and positive predictive values of 97% and 95%, respectively, for the development of diabetes in the Oji-Cree by 50 years of age. This makes the HNF1A G319S genotype the most specific predictive genetic test for diabetes in any human population. HNF1A S319 has all the attributes of a thrifty allele in the Oji-Cree. It is possible that the recent increase in CHD in the aboriginal people of northern Ontario is the result of the expression of diabetes susceptibility due to HNF1A S319 as a consequence of rapid changes in environment and lifestyle.
在过去20年里，安大略省北部原住民中冠心病（CHD）的发病率增长了两倍。这与这些原住民社区中2型糖尿病的极高患病率有着千丝万缕的联系。安大略省北部约40%的奥吉-克里人患有典型的与肥胖相关的2型糖尿病，这与50年前几乎无病例报告的情况相比有了急剧增长。奥吉-克里人在肝细胞核因子1α（HNF1A）基因中存在一个特定突变，即G319S，其他种族群体和原住民中均不存在该突变。HNF1A S319是糖尿病易感等位基因，最有说服力的原因在于它与糖尿病的存在及严重程度始终存在统计学关联。此外，对于50岁时奥吉-克里人患糖尿病的情况，HNF1A S319的特异性和阳性预测值分别为97%和95%。这使得HNF1A G319S基因型成为任何人群中对糖尿病最具特异性的预测性基因检测。在奥吉-克里人中，HNF1A S319具备节俭型等位基因的所有特征。安大略省北部原住民中近期冠心病发病率的上升，可能是由于环境和生活方式的快速变化，导致HNF1A S319引发糖尿病易感性的结果。
