MODY6基因在家族性2型糖尿病发病中的作用  

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

作　　者：韩学尧[1] 刘春雁[1] 纪立农[1] 

机构地区：[1]北京大学人民医院内分泌科北京大学糖尿病中心,100044

出　　处：《中华医学杂志》2005年第35期2463-2467,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30270623);国家高技术研究发展计划基因项目资助(2002AA223031)

摘　　要：目的探讨NeuroD1/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NeuroD1/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。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-β 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.

关 键 词：糖尿病 非胰岛素依赖型 基因 结构 2型糖尿病发病 家族性 6基因 MODY BETA2基因 NeuroD1 DNA序列分析 糖尿病家系 

分 类 号：R587.1[医药卫生—内分泌]