小儿肾病综合征血管紧张素Ⅰ转换酶基因多态性的研究

Angiotensin Ⅰ-converting enzyme gene polymorphism in children with nephrotic syndrome

目的 探讨血管紧张素Ⅰ转换酶 (ACE)基因多态性在不同激素效应和病理改变的原发性肾病综合征 (NS)患儿中的分布及意义。方法 用聚合酶链反应 (PCR)分别检测 10 7例健康儿童和42例NS患儿的ACE基因 ,并同时用紫外法分别测定血清ACE的活性。结果 (1)NS患儿激素部分效应及无效应组的DD型基因频率为 6 0 % ,与激素完全效应组 (5 % )比较差异有显著意义 (P <0 .0 1)。(2 )肾活检 15例中局灶节段性硬化 (FSGS)的病理改变者 6例 ,其中ID基因型 1例 ,DD基因型 5例 ,无II基因型 ;non FSGS病理改变者 9例 ,其中II基因 5例 ,ID基因 3例 ,DD基因 1例。两组各基因型分布比较显示 :FSGS组以DD型为主 (与non FSGS组比较P =0 .0 0 19) ,non FSGS组以II型为主 (与FSGS组比较P =0 .0 419)。 (3)正常儿童ACE的活性为 (2 5± 17)U/L ,NS患儿血清ACE的活性为 (2 8± 18)U/L ,两组比较差异无显著意义 (t=1.0 7,P >0 .0 5 ) ;但每组不同基因型之间血清ACE活性差异均有显著意义 (正常组F =2 9.0 1,NS组F =6 5 .5 6 ;P均 <0 .0 1)。 (4)激素完全效应者的血清ACE活性为 (13± 3)U/L ,激素无效应及部分效应者血清ACE活性为 (18± 4)U/L ,两组比较差异有显著性意义 (t=3.0 9,P <0 .0 1)。 (5 )FSGS患儿血清的ACE活性为 (38± 10 )

Objective To investigate the correlation between angiotensin I converting enzyme (ACE) gene polymorphism and nephrotic syndrome (NS) in children. Methods The ACE genotype of 42 children with NS and 107 healthy controls was detected by using polymerase chain reaction (PCR). Serum ACE activity was measured by ultraviolet assay at the same time. Results (1) The distribution of ACE DD genotype was significantly different between the groups poorly and well responded to corticosteroid therapy (60 % vs. 5 %, P <0.01). (2) Of 15 cases in whom renal biopsy was performed, 6 had pathological changes of focal segmental glomerular sclerosis (FSGS), of whom 1 case had genotype ID, 5 had genotype DD, i.e., none of the 6 cases had genotype II; of the 9 cases without FSGS pathological changes, 5 had genotype II, 3 had genotype ID and 1 had genotype DD. Comparison of genotype distribution between the 2 groups showed that genotype DD dominated the FSGS group ( P =0.0019 compared with the non FSGS group), while genotype II dominated the non FSGS group ( P =0.0419 compared with FSGS group). (3) The serum ACE activity showed no difference between the patient group and control group (28±18 U/L vs. 25±17 U/L, P >0.05). But the activity was significantly different among different genotypes within each of the 2 groups (F=29.01 for the control group and F=65.56 for NS group, P <0.01 for both groups). (4) The serum ACE activity showed significant difference between the groups poorly and well responded to corticosteroid therapy (18±4 U/L vs. 13±3 U/L; t =3.09, P <0.01). (5) The serum ACE activity was significantly different between children with FSGS and children without FSGS (38±10 U/L vs. 23±12 U/L; t =2.18, P <0.05). Conclusions (1) Genotype DD is associated with poor responsiveness to corticosteroid therapy and FSGS in NS children. (2) The NS patients with genotype DD had the highest serum ACE activity and those with genotype II had the lowest. (3) The higher serum ACE activity was associated with poor responsiveness to corticosteroid therapy and FSGS in NS children.