【摘要】 目的早发2型糖尿病家系中可能存在MODY2基因(GCK)的致病突变,了解MODY2基因在早发家族性2型糖尿病发病中作用。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,且至少还有一个一级亲属在45岁之前被诊断糖尿病。提取先证者血DNA,用PCR产物扩增MODY2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。SPSS进行统计分析。结果在MODY2基因的筛查中发现3个DNA变异,一个在外显子4(ccc-ccg,为杂合的脯氨酸同义突变Pro145Pro),一个在外显子7(gcc-gcg,为杂合的丙氨酸同义突变ala233 ala),一个在内含子9(IVS+8C>T)。这三个变异等位基因频率分别为0.5%、0.5%、36%。对内含子IVS9+8C>T多态性的群体关联研究发现等位基因T在糖尿病组频率显著低于非糖尿病对照组(36%vs 47%,P<0.05),而C等位基因高于对照组(64%vs 53%,P<0.05)。结论MODY2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。更多还原

【Abstract】 Objective To explore the disease-associated gene mutations in early onset familial type 2 diabetes containing subjects with MODY2(GCK).Methods We collected 100 early onset type 2 diabetes pedigrees,in which the probands were diagnosed as type 2 diabetes before 40 years old and,at least,another first relatives was diagnosed as type 2 diabetes before 45 years old.By PCR,all the exons and(exon/intron) splice sites of MODY2 gene were amplified and PCR products were sequenced to identify the DNA variants.Results In our study we observed three DNA vatiants in MODY2 gene: one in exon4(ccc-ccg,heterozygous silent mutation,pro145pro),one in exon7(gcc-gcg,heterozygous silent mutation,ala233ala),and one in intron 9(IVS+8 C>T).The prevalences of these variant alleles were 0.5% in exon4,0.5% in exon 7 and 36% in intron 9.An association study was conducted to examine the relationship between the IVS9+8 C>T polymorphism and early onset familial type 2 diabetes,the frequence of allele T of early onset familial type 2 diabetes population was significantly lower36% vs 47%,P<0.05,and the frequency of allele C significantly higher,than that of control subjects(64% vs 53%,P<(0.05)).Conclusion There is no enough evidence to demonstrate that the variation in or near MODY2 genes is the major cause of early onset type 2 diabetic in Chinese population.更多还原