激素耐药型肾病综合征儿童与COL4A5基因突变的关系研究

Study on the relationship between COL4A5 gene mutation and steroid-resistant nephrotic syndrome

目的探讨糖皮质激素(激素)耐药型肾病综合征(SRNS)儿童与Ⅳ型胶原A5(COL4A5)基因突变的关系。方法选取51例原发性肾病综合征(PNS)患儿,其中经足量激素治疗4周无效的患儿即SRNS 26例,经足量激素治疗4周有效的患儿即激素敏感型NS(SSNS)25例,并选择同期体检的27名健康儿童作对照,采集外周血提取DNA,并进行DNA测序。结果COL4A5基因突变仅在PNS患儿中检出而在对照组中未检出。51例PNS患儿中,检出COL4A5基因突变16例,其中散发突变和遗传突变各8例。SRNS患儿的COL4A5基因突变检出率为46%,高于SSNS患儿的16%(P<0.05)。SRNS患儿和SSNS患儿的突变来源比较差异无统计学意义(P>0.05)。结论COL4A5基因突变和PNS的发生有关,且该突变可能与患儿激素耐药有关。

Objective To investigate the relationship between steroid-resistant nephrotic syndrome(SRNS)and typeⅣcollagen alpha 5(COL4A5)gene mutation in children.Methods A total of 51 children with primary nephrotic syndrome(PNS)were enrolled.Twenty-six children who were not healed after 4-week adequate hormone therapy were assigned into the SRNS group,25 patients who were effectively treated with adequate hormone therapy were allocated into the steroid-sensitive NS(SSNS)group,and 27 healthy children receiving physical examination were recruited as normal controls.DNA was extracted from the peripheral blood of PNS and healthy children.DNA sequencing was performed.Results COL4A5 gene mutation was detected in the PNS children rather than the normal controls.Among 51 PNS children,COL4A5 gene mutation was identified in 16 children including 8 cases of sporadic and 8 cases of genetic mutations.The COL4A5 gene mutation rate in the SRNS group was 46%,significantly higher compared with 16%in the SSNS group(P<0.05).The source of mutation did not significantly differ between the SRNS and SSNS children(P>0.05).Conclusion The COL4A5 gene mutation is closely correlated with the occurrence of PNS,which is probably associated with the steroid resistance in children.