Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Arch Pharm Res. 2013 Feb;36(2):167-77. doi: 10.1007/s12272-013-0021-x. Epub 2013 Feb 2.
Type 2 diabetes (T2DM) is a common complex metabolic disorder that has a strong genetic component. Recent advances in genome-wide association studies have revolutionized our knowledge regarding the genetics of T2DM. There are at least 64 common genetic variants that are strongly associated with T2DM. However, the pathophysiologic roles of these variants are mostly unknown and require further functional characterization. The variants identified so far have a small effect size and their added effect explains less than 10 % of the T2DM heritability. The current ongoing whole exome and whole genome studies of T2DM are focused on identifying functionally important rare variants that have a stronger effect. Through these efforts, we will have a better understanding of the genetic architecture of T2DM and its pathophysiology. The potential clinical applications of genetic studies of T2DM include risk prediction, identification of novel therapeutic targets, genetic prediction of efficacy and toxicity of anti-diabetic medications, and eventually optimization of patient care through personalized genomic medicine. We hope further research in genetics of T2DM could aid patient care and improve outcomes of T2DM patients.
2 型糖尿病(T2DM)是一种常见的复杂代谢紊乱疾病,具有很强的遗传成分。全基因组关联研究的最新进展彻底改变了我们对 T2DM 遗传学的认识。至少有 64 个常见的遗传变异与 T2DM 强烈相关。然而,这些变异的病理生理作用大多未知,需要进一步进行功能特征分析。迄今为止发现的变异体效应较小,其附加效应仅能解释 T2DM 遗传率的不到 10%。目前正在进行的 T2DM 全外显子组和全基因组研究侧重于鉴定具有更强效应的功能重要的罕见变异体。通过这些努力,我们将更好地了解 T2DM 的遗传结构及其病理生理学。T2DM 遗传研究的潜在临床应用包括风险预测、新治疗靶点的鉴定、抗糖尿病药物疗效和毒性的遗传预测,以及最终通过个性化基因组医学优化患者治疗。我们希望进一步研究 T2DM 的遗传学能够有助于改善患者的护理并提高 T2DM 患者的治疗效果。