中国人早发及多发糖尿病家系中筛查胰岛素启动因子1基因突变

Screening insulin promoter factor 1 gene mutation in Chinese early-onset and/or multiplex diabetes pedigrees

目的 观察中国人早发及多发糖尿病家系胰岛素启动因子 1(IPF1)基因的变异情况。方法 采用PCR SSCP方法筛查 15 4例早发及多发糖尿病家系先证者IPF1基因突变。采用PCR RFLP方法检测突变家系其他成员及两组正常对照的该突变位点。结果 在多发糖尿病家系先证者中发现 1例P2 39Q错义突变 ,该家系另有 6人携带此突变 ,且口服葡萄糖耐量试验均在正常范围。P2 39Q突变未与糖尿病表型共分离。非糖尿病突变携带者餐后 2h血糖水平明显高于非突变携带者 (P =0 .0 2 4 9)。在“超正常”对照中亦检出 1例P2 39Q突变 ,中国人糖尿病家系组和正常对照组突变频率分别为 0 .6 %及 0 .5 %。此频率与斯堪的纳维亚人群相似。结论 尽管IPF1基因突变不是中国人早发及多发糖尿病的主要致病基因 ,但IPF1基因P2 39Q突变可致轻度糖代谢紊乱 。

Objective To screen the insulin promoter factor 1 (IPF1) gene mutation in Chinese pedigree with early-onset and/or multiplex diabetes.Methods 154 unrelated probands from early-onset and/or multiplex diabetes pedigrees were screened for IPF1 gene mutations using PCR-SSCP and DNA sequencing. PCR-RFLP was performed to examine the prevalence of the mutation in two non-diabetic groups and the family members of the proband carrying the mutation.Results One missense mutation, P239Q, was identified in one of the 154 probands. Six family members of the proband, whose glucose tolerance was normaly carried this mutation. The 2h plasma glucose level in the non-diabetic mutation carriers was significantly higher than that in the non-mutated subjects (P= 0.024 9). The P239Q mutation was also detected in one of the 93 supernormal controls. The frequencies of the mutation in DM groups and ND groups ( 0.6% and 0.5% respectively) were similar to that of Scandinavians.Conclusion Although IPF1 gene mutation is not a major cause of early-onset and/or multiplex diabetes families in the Chinese population, the P239Q mutation of IPF1 gene may have mild glucose disturbance and contribute to the development of diabetes in the presence of other genetic and environmental factors.