Hansen L, Jensen J N, Urioste S, Petersen H V, Pociot F, Eiberg H, Kristiansen O P, Hansen T, Serup P, Nerup J, Pedersen O
Steno Diabetes Center, Panum Institute, University of Copenhagen, Denmark.
Diabetes. 2000 May;49(5):876-8. doi: 10.2337/diabetes.49.5.876.
Mutations in the NeuroD/BETA2 gene have been shown to associate with type 2 diabetes. In the present study, we examined mutations in the NeuroD/BETA2 gene for association with either type 1 or 2 diabetes. Three variants were identified in patients with type 2 diabetes: Ala45Thr (allelic frequency 0.36, 95% CI 0.31-0.41), Pro197His (0.01), and Ser259Ser (0.01). Ala45Thr and Pro197His were not associated with type 2 diabetes, but the transmission disequilibrium test showed unequal transmission of the A45 allele to offspring with type 1 diabetes (chi2 = 5.90, P < 0.02, odds ratio 1.55, 95% CI 0.91-2.63). This association could not be explained by linkage disequilibrium between the Ala45 allele and IDDM7 (D2S152), which is also located on chromosome 2q32. When tested in vitro, the biological activity of Thr45 (117+/-36% vs. Ala45) and His197 (90+/-28% vs. Pro197) on the regulation of the human insulin gene promoter appeared normal. In conclusion, mutations in the NeuroD/BETA2 gene are not a common cause of late-onset type 2 diabetes among Danes. However, in the type 1 diabetic Danish population, the Ala45Thr variant of NeuroD/BETA2 may represent a susceptibility marker independent of IDDM7 on chromosome 2q32.
已证实NeuroD/BETA2基因的突变与2型糖尿病相关。在本研究中，我们检测了NeuroD/BETA2基因的突变与1型或2型糖尿病的相关性。在2型糖尿病患者中鉴定出三个变异：Ala45Thr（等位基因频率0.36，95%可信区间0.31 - 0.41）、Pro197His（0.01）和Ser259Ser（0.01）。Ala45Thr和Pro197His与2型糖尿病无关，但传递不平衡检验显示A45等位基因向1型糖尿病后代的传递不均衡（χ2 = 5.90，P < 0.02，优势比1.55，95%可信区间0.91 - 2.63）。这种关联不能用同样位于2号染色体2q32的Ala45等位基因与IDDM7（D2S152）之间的连锁不平衡来解释。在体外检测时，Thr45（117±36% vs. Ala45）和His197（90±28% vs. Pro197）对人胰岛素基因启动子的调节作用的生物学活性似乎正常。总之，NeuroD/BETA2基因的突变不是丹麦人晚发型2型糖尿病的常见病因。然而，在丹麦1型糖尿病患者群体中，NeuroD/BETA2基因的Ala45Thr变异可能代表一种独立于2号染色体2q32上IDDM7的易感标记。
