摘要目的 基于补体因子H(complement factor H,CFH)在糖尿病患者中的高表达以及补体因子H相关蛋白1(complement factor H related protein 1,CFHR1)序列和功能与CFH的相似性,探讨2型糖尿病患者在CFHR1的表达量及其基因序列多态性方面的差异.方法 选取2型糖尿病患者50例,健康对照者30名.对其血浆样品在前处理后进行多肽脱胶电泳,利用Nano HPLC-Chip-MS/MS系统对按等电点分离的多肽样品进行进一步的分离和质谱鉴定,筛选差异蛋白质.应用酶联免疫吸附实验法对CFHR1蛋白的表达量进行测定.提取样本的基因组DNA,对CFHR1基因的6个外显子进行扩增和测序,比较其多态性位点的差异.结果 经酶联免疫吸附实验法验证,糖尿病患者血浆中的CFHR1表达量显著高于健康对照者(P=2.78×1011).CFHR1基因第5外显子的rs12406079位点的等位基因频率在对照组和糖尿病组之间的差异具有统计学意义(x2=5.692,P=0.017).结论 CFHR1的表达量及其基因多态性位点在糖尿病患者和健康对照者之间存在明显差异,CFHR1可能与2型糖尿病相关.

abstractsObjective To explore the characteristics in CFHR1 concentration and the frequency of CFHR1 gene polymorphisms of patients with type 2 diabetes mellitus (T2DM) based on the high level of complement factor H (CFH) expression among such patients and the similarity between CFHR1 and CFH in terms of sequence and functions.Methods Fifty T2DM patients and 30 healthy controls were selected.The plasma samples were separated by pI with OFFGEL electrophoresis following solution digestion.Further separation and identification were carried out on a Nano HPLC-Chip-MS/MS system,Differentially expressed proteins were identified by comparison.Enzyme-linked immunosorbent assay (ELISA) was used to validate the result.Genomic DNA of the two groups was extracted.Polymerase chain reaction and sequencing were used to determine the single nucleotide polymorphisms in the 6 exons of the CFHR1 gene.Results The CFHR1 level in plasma of T2DM patients were significantly higher than that of the healthy controls (P=2.78 × 10-n).A significant difference in allelic frequencies of rs12406079 of the fifth exon of the CFHR1 gene was found between the two groups (x2 =5.692,P =0.017).Conclusion The concentration of CFHR1 and frequencies of CFHR1 gene polymorphisms among patients with T2DM differ significantly from healthy subjects.Polymorphisms of the CFHR1 gene are associated with T2DM.