Kleinberger Jeffrey W, Pollin Toni I
Division of Endocrinology, Diabetes, and Nutrition and Program in Personalized and Genomic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
Ann N Y Acad Sci. 2015 Jun;1346(1):45-56. doi: 10.1111/nyas.12757. Epub 2015 Apr 23.
Diabetes mellitus affects approximately 382 million individuals worldwide and is a leading cause of morbidity and mortality. Over 40 and nearly 80 genetic loci influencing susceptibility to type 1 and type 2 diabetes, respectively, have been identified. In addition, there is emerging evidence that some genetic variants help to predict response to treatment. Other variants confer apparent protection from diabetes or its complications and may lead to development of novel treatment approaches. Currently, there is clear clinical utility to genetic testing to find the at least 1% of diabetic individuals who have monogenic diabetes (e.g., maturity-onset diabetes of the young and KATP channel neonatal diabetes). Diagnosing many of these currently underdiagnosed types of diabetes enables personalized treatment, resulting in improved and less invasive glucose control, better prediction of prognosis, and enhanced familial risk assessment. Efforts to enhance the rate of detection, diagnosis, and personalized treatment of individuals with monogenic diabetes should set the stage for effective clinical translation of current genetic, pharmacogenetic, and pharmacogenomic research of more complex forms of diabetes.
全球约有3.82亿人受糖尿病影响，糖尿病是发病和死亡的主要原因。目前已分别确定了40多个和近80个影响1型和2型糖尿病易感性的基因位点。此外，越来越多的证据表明，一些基因变异有助于预测治疗反应。其他变异则明显能预防糖尿病及其并发症，可能会带来新的治疗方法。目前，基因检测具有明确的临床应用价值，可用于找出至少1%患有单基因糖尿病的糖尿病患者（例如，青年发病的成年型糖尿病和KATP通道新生儿糖尿病）。诊断出许多目前诊断不足的糖尿病类型可实现个性化治疗，从而改善血糖控制，减少侵入性，更好地预测预后，并加强家族风险评估。提高单基因糖尿病患者的检测、诊断和个性化治疗率的努力应为目前对更复杂形式糖尿病的基因、药物遗传学和药物基因组学研究的有效临床转化奠定基础。
