【摘要】 目的 研究结缔组织生长因子基因启动子多态性及其与上海地区中国人IgA肾病发生的相关性。方法 应用聚合酶链反应(PCR)-PCR产物直接测序技术,对50例IgA肾病(IgAN)患者和30例健康对照者(包括28例中国人和2例白种人)进行结缔组织生长因子基因ccn2(ctgf)启动子多态性研究。结果 检测到1种多态和1种突变。多态性改变G-447/C位于ccn2基因启动子的骨髓锌指蛋白(MZF)1结合基序附近。50例IgAN患者中有G-447/C多态性2例(4％);28例中国健康对照者中有1例(3.57％),该多态性频率两组间差异无显著性意义。在1例IgAN患者中发现ccn2基因1号外显子第20位核苷酸处存在G→T颠换,该突变接近ccn2基因mRNA的5’端帽式结构区,30例正常人中未发现这种突变。结论 (1)中国人群中有ccn2基因启动子多态性存在,ccn2基因启动子G-447/C多态性可能与IgAN发生无直接相关。(2)IgAN患者中存在ccn2基因1号外显子5’非编码区G→T颠换。经检索,该突变属首次报道。更多还原

【Abstract】 Objective To investigate whether the promoter region of the ccn2 (ctgf) contains polymorphic sequences that might account for the pathogenicity of IgA nephropathy (IgAN) . Methods Eighty human DNA samples, 50 patients with IgAN and 30 healthy control, were screened for ccn2 (ctgf) promoter polymorphism, using polymerase chain reaction (PCR ) and DNA sequencing. Results One polymorphism and one mutation were identified in these subjects. A G to C polymorphism was found at position-447 which is thought to lie nearby predicted binding domains for the transcription factor MZF1. The G-447/C polymorphism was found in two of 50 patients and one of 28 Chinese control subjects(except two whites), respectively. The frequencies of genotypes GG and GC in patients with IgAN (96% vs 4% ) and in control subjects (96. 43% vs 3. 57% ) were not significantly different. No CC genotype was detected in all of the samples. Moreover, a novel G to T substitution at position 20 in exon 1 of ccn2 (ctgf) gene was found in one of IgAN patients and none in controls. This G/T mutation, reported for the first time, lay adjacent to 5’ -end cap of mRNA. Conclusions (1) Sequence analysis of the ccn2 (ctgf) promoter reveals one polymorphic site in Shanghai Chinese population and this G-447/C polymorphism may not be directly associated with the occurrence of IgAN. (2) A G to T substitution at position 20 in exon 1 of ccn2 (ctgf) gene is found in one of patients with IgAN. It is reported for the first time.更多还原