中国人早发及多发糖尿病家系中HNF4A基因突变的筛查

目的探讨中国上海及周边地区早发及（或）多发糖尿病家系肝细胞核因子如基因（hepatocyte nuclear faetor-4α，HNF4A）的突变及变异发生情况。方法用PER-单链构象多态及序列分析的方法对154例早发及（或）多发糖尿病家系先证者进行HNF4A基因扫查。对发现的突变或变异采用PCR-限制性片段长度多态性方法在家系其他成员及93名正常对照者中进一步检测。结果在2例糖尿病家系先证者中发现2个同义突变，即N153N和A158A。其中N153N在1个早发性糖尿病家系中见到，且与糖尿病共分离。上述同义突变在正常者中未查到。此外，还发现3个变异位点：即IVS1＋308（A→G）（rs2071197），IVS1＋357（A→T）（rs2071198），IVS1-5（C→T）（rs745975）。3个位点基因型和等位基因频率在糖尿病先证者和正常对照者中无品著差别．结论HNF4A基因突变在中国人早发及（或）多发糖尿病家系中可能罕见。

Scanning the HNF4A gene mutation from Chinese pedigrees with early- and/or multiple-onset diabetes

OBJECTIVE: To screen the mutation of hepatocyte nuclear factor 4 alpha gene (HNF4A) in Chinese pedigrees with early and/or multiplex-onset diabetes in Shanghai and nearby area. METHODS: By PCR-single strand conformation polymorphism (PCR-SSCP) and direct sequencing, the mutation screen of HNF4A gene was performed in 93 normal controls and 154 unrelated probands from early- and/or multiplex-onset diabetes. The PCR-RFLP was used to analyze the frequencies of the discovered mutations and variants. RESULTS: Two synonymous mutations (N153N, A158A) were found in two families, of which the N153N was co-segregated with early-onset diabetes. These two synonymous mutations were not detected in the 93 normal controls. Three variants, IVS1+308(A to G)(rs2071197), IVS1+357(A to T)(rs2071198), IVS1-5(C to T)(rs745975), were also identified in this study. The genotype and allele frequencies of the three variants had no difference between the probands and normal controls. CONCLUSION: HNF4A gene mutation is rare in Chinese pedigrees with early and/or multiplex-onset diabetes.