Doria Alessandro, Patti Mary-Elizabeth, Kahn C Ronald
Joslin Diabetes Center, One Joslin Place, Harvard Medical School, Boston, MA 02215, USA.
Cell Metab. 2008 Sep;8(3):186-200. doi: 10.1016/j.cmet.2008.08.006.
Type 2 diabetes is a genetically heterogeneous disease, with several relatively rare monogenic forms and a number of more common forms resulting from a complex interaction of genetic and environmental factors. Previous studies using a candidate gene approach, family linkage studies, and gene expression profiling uncovered a number of type 2 genes, but the genetic basis of common type 2 diabetes remained unknown. Recently, a new window has opened on defining potential type 2 diabetes genes through genome-wide SNP association studies of very large populations of individuals with diabetes. This review explores the pathway leading to discovery of these genetic effects, the impact of these genetic loci on diabetes risk, the potential mechanisms of action of the genes to alter glucose homeostasis, and the limitations of these studies in defining the role of genetics in this important disease.
2型糖尿病是一种基因异质性疾病，有几种相对罕见的单基因形式以及一些由遗传和环境因素复杂相互作用导致的更常见形式。以往使用候选基因方法、家族连锁研究和基因表达谱分析的研究发现了一些2型糖尿病相关基因，但常见2型糖尿病的遗传基础仍不清楚。最近，通过对大量糖尿病患者群体进行全基因组单核苷酸多态性（SNP）关联研究，为确定潜在的2型糖尿病基因打开了一扇新窗口。本综述探讨了导致发现这些遗传效应的途径、这些基因座对糖尿病风险的影响、基因改变葡萄糖稳态的潜在作用机制，以及这些研究在确定遗传学在这一重要疾病中的作用方面的局限性。
