北京地区早发糖尿病家系MODY5基因突变的筛查

目的 了解年轻起病成人型糖尿病(maturity-onset diabetes of the young,MODY)基因(HNF-1 β)在早发家族性2型糖尿病发病中的作用.方法 收集100个2型糖尿病家系,先证者均在40岁前被诊断为糖尿病,且至少还有1个一级亲属在45岁之前被诊断糖尿病.提取先证者血DNA,用PCR产物扩增MODY5基因的所有外显子和外显子/内含子拼接区,将PCR产物直接进行测序.另选100名非糖尿病者为对照.结果 在MODY5基因的筛查中发现2个非编码区的DNA变异IVS8 42 G＞A,IVS9-22 C＞T及1个编码区的变异ExonA513T.而对100名非糖尿病对照组进行DNA测序未发现此变异.结论 MODY5基因内或附近的基因变异不是早发2型糖尿病家系的主要致病原因.在新发现的MODY5基因变异中(A513T),有可能是一个疾病关联突变,但具体致病机制有待蛋白质功能研究证实.

Molecular scanning for MODY5 mutation in Beijing population of familial early-onset type 2 diabetes

Objective To explore the disease-associated gene(MODY5) mutations in familial early-onset type 2 diabetes.Methods One hundred pedigrees of early-onset type 2 diabetes were collected in Beijing,of which the probands were diagnosed as type 2 diabetes under 40 years old and,at least,another first relatives was diagnosed as type 2 diabetes under 45 years old.Another 100 non-diabetic subjects were enrolled as controls.By PCR,all the exons and exon/intron splice sites of MODY5 gene were amplified and PCR products were sequenced to identify the DNA variants.Results By screening MODY5 gene,2 DNA variants were identified in noncoding region including IVS8 42G>A,IVS9-22C>T,1 mutation in coding region including A513T. No target gene mutations were found in 100 controls.Conclusion No enough evidence demonstrates that the variation in or near MODY5 genes is the major cause of early-onset type 2 diabetes in Beijing population.A novel mutation of MODY5 gene was found to possibly relate to diabetes,which mechanism needs to be proved by further study of protein function.