原发性肾病综合征患儿血管紧张素原和血管紧张素转换酶基因多态性的检测与临床分析

目的探讨北方汉族原发肾病综合征(PNS)儿童血管紧张素原(AGT)基因M235T单核苷酸与血管紧张素转换酶(ACE)基因多态性的关系。方法研究对象为2001—2005年首都医科大学附属儿童医院住院的148例北方汉族PNS患儿及50例正常儿童，采用聚合酶链反应-限制性片段长度多态性方法检测AGT(M235T)、ACE(I/D)的多态性。结果PNS组携带ACE基因DD型、D等位基因、AGT基因MT型及同时携带D、T等位基因的频率高于正常对照组(P分别为0.004、0.032、0.036、0.004)。复发组D等位基因频率高于非复发组(P=0.000)。PNS患儿中高胆固醇+高三酰甘油(甘油三脂)血症组DD基因频率高于正常组(P=0.006)。激素耐药组DD基因频率(34.21%)高于激素敏感组(20.91%)。ACE基因的插入序列长度为289bp，存在2处单核苷酸多态性，分别为第103、151位各插入1个G。结论携带ACE基因D等位基因、AGT基因MT型、同时携带D(DD/ID)、T(MT/TT)等位基因的北方汉族儿童为PNS的易感人群。携带ACE(DD)基因PNS患儿易复发、可能易合并高胆固醇及高三酰甘油血症，可能会有激素耐药倾向。ACE基因插入序列长度及核苷酸序列与国外报道不同。

Research on AGT(M235T) and ACE(I/D) gene polymorphisms in children with primary nephrotic syndrome.

AbstractObjectiveTo investigate angiotensinogen(AGT) M235T and angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms,and their effects on clinical features of northern Han nationality children with primary nephrotic syndrome (PNS).MethodsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques was used to identify the AGT(M235T) and ACE(I/D) gene polymorphisms in 148 northern Han nationality children with PNS and 50 children as control group.ResultsThe ACE DD genotype,D allele and the AGT MT genotype frequencies were significantly higher in PNS group than that in the control group(P=0.004,0.032,0.036).The ratio of the patients with D and T genotype simultaneously was also higher(P=0.004).D allele frequency was significantly higher in PNS patients with relapse than that of the patients without relapse(P=0.000).The ACE DD genotype frequency was higher in steroid-resistant PNS than the steroid responsive PNS(34.21% vs 20.91%).The ACE DD genotype frequency was higher in patients with both hypercholesterolemia and hypertriglyceridemia than the control group (P=0.006).The lengths of the inserted gene sequence of ACE gene was 289bp.There were several nucleotides polymorphisms of the inserted sequence.They were at position 103 and 151;one G was inserted separately.ConclusionNorthern Han nationality children with ACE(D allele) genotype,with AGT(MT) genotype,with both D allele of ACE gene and T allele of AGT gene simultaneously may correlate with a predisposing factor for PNS.Patients with DD genotype may have much higher risk of relapse,hypercholesterolemia and hypertriglyceridemia and steroid resistence.The length of the inserted gene of ACE is 289bp,and the necleotide sequence is somewhat different from that of foreign countries.