MODY6基因在家族性2型糖尿病发病中的作用

目的探讨NeumD1／BETA2基因在中国北方地区家族性2型糖尿病发病中的作用。方法用PCR和单链构像多态性技术（PCR—SSCP）对188名2型糖尿病家系的先证者NeuroD1／BETA2基因的编码区序列进行突变筛查,对发现的变异进行DNA序列分析证实,并对130名正常人进行基因分型,比较两组的等位基因、基因型频率和临床表型的差别。结果在NeuroD1／BETA2基因的筛查中发现多态性A45T和突变Gly12Arg,其中A45T在病人和正常人中的频率分别是19．7％和10％,差异有统计学意义（P〈0．05）,在正常对照组发现携带A45T的个体比A45A个体有较低的B细胞功能。仅在一个家系中发现Gly12Arg突变,且与糖尿病共分离。在正常人未筛查到此突变。结论NeumD1／BETA2基因的多态性A45T在中国人群的家族性2型糖尿病相关,NeuroD1／BETA2基因或附近的基因与中国人群家族性2型糖尿病的发病中起一定的作用,而Gly12Arg可能是导致糖尿病的突变。

Contribution of MODY6 gene in the pathogenesis of familial type 2 diabetes in Chinese population

OBJECTIVE: To investigate the contribution of MODY6 gene in the pathogenesis of familiar type 2 diabetes in Chinese population. METHODS: PCR and single strand configuration polymorphism (PCR-SSCP) technique was used to screen the coding sequence of NeuroD1/BETA2 gene for DNA variants in 188 probands in the pedigrees of familiar type 2 diabetes and 130 normal persons as controls in Beijing, China. The discovered variants were confirmed by sequencing. RESULTS: A4T5 polymorphism and a novel Gly12Arg mutation were found. The frequency of A4T5 of the patients was 19.7%, significantly higher than that of the controls (10.0%, P < 0.05). In the control group, the Homa-beta of the 13 subjects with T allele was 4.6 +/- 04, significantly lower than that of the 117 subjects without T allele (4.9 +/- 0.5, P < 0.05). Co-segregating with diabetes, Gly12Arg mutation was found in only one pedigree and in none normal subjects. CONCLUSION: A4T5 polymorphism of NeuroD1/BETA2 gene is correlated with familiar type 2 diabetes in Chinese population. NeuroD1/BETA2 gene or its nearby gene may play a role in the pathogenesis of familiar type 2 diabetes. The novel GlyArg mutation may be a genetic cause of some diabetic pedigrees.