白细胞介素-10基因G-1082A多态性与原发性肾小球肾炎进展的相关性

Association of interleukin-10 gene G-1082A polymorphism with the progression of primary glomerulonephritis.

作者信息

Bantis Christos, Heering Peter J, Aker Sendogan, Klein-Vehne Nicola, Grabensee Bernd, Ivens Katrin

机构信息

Department of Nephrology and Rheumatology, Heinrich-Heine University, Düsseldorf, Germany.

出版信息

Kidney Int. 2004 Jul;66(1):288-94. doi: 10.1111/j.1523-1755.2004.00730.x.

DOI:10.1111/j.1523-1755.2004.00730.x

PMID:15200436

Abstract

BACKGROUND

Interleukin-10 (IL-10) is a cytokine with immunosuppressive properties. We evaluated the influence of G-1082A polymorphism in the IL-10 gene promoter, which has been associated with modified IL-10 production, on the two most common forms of primary glomerulonephritis: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS).

METHODS

We studied Caucasian patients (N= 191) with biopsy-proven glomerulonephritis (IgAN: N= 123, FSGS: N= 68) followed-up for 6.5 +/- 5.5 years. Patients were classified according to the slope of reciprocal serum creatinine (>/= or <-0.1 dL()mg(-1) ()year(-1)) into group A (slow progressors, IgAN: N= 75, FSGS: N= 47) and group B (fast progressors, IgAN: N= 48, FSGS: N= 21). One hundred healthy volunteers were analyzed as control patients. G-1082A polymorphism was determined by polymerase chain reaction (PCR) amplification.

RESULTS

The allele frequencies were similar in patients and control group (NS). Initial renal function, proteinuria, and blood pressure did not differ significantly between patients with different genotypes. G-1082A polymorphism was associated with the progression of both IgAN and FSGS: GA/AA genotypes were more frequent in group B (fast progressors) than in group A (slow progressors; P= 0.012 for IgAN, P < 0.05 for FSGS). Patients with the GA/AA genotypes showed a worse outcome in the Kaplan-Meier analysis of renal survival (P < 0.05 for both IgAN and FSGS). The IL-10 polymorphism remained an independent risk factor for progression in multivariate analysis (Cox regression model, P < 0.05 for IgAN and FSGS).

CONCLUSION

Our results suggest that IL-10 gene G-1082A polymorphism is an important marker of progression in patients with IgAN and FSGS.

摘要

背景

白细胞介素-10（IL-10）是一种具有免疫抑制特性的细胞因子。我们评估了IL-10基因启动子中的G-1082A多态性（其与IL-10产生的改变有关）对原发性肾小球肾炎的两种最常见形式：IgA肾病（IgAN）和局灶节段性肾小球硬化（FSGS）的影响。

方法

我们研究了经活检证实患有肾小球肾炎的白种人患者（N = 191）（IgAN：N = 123，FSGS：N = 68），随访时间为6.5±5.5年。根据血清肌酐倒数的斜率（≥或≤-0.1 dLmg⁻¹年⁻¹）将患者分为A组（进展缓慢者，IgAN：N = 75，FSGS：N = 47）和B组（进展快速者，IgAN：N = 48，FSGS：N = 21）。分析100名健康志愿者作为对照患者。通过聚合酶链反应（PCR）扩增确定G-1082A多态性。

结果

患者组和对照组的等位基因频率相似（无显著性差异）。不同基因型患者的初始肾功能、蛋白尿和血压无显著差异。G-1082A多态性与IgAN和FSGS的进展均相关：B组（进展快速者）中GA/AA基因型比A组（进展缓慢者）更常见（IgAN中P = 0.012，FSGS中P < 0.05）。在肾脏生存的Kaplan-Meier分析中，GA/AA基因型患者的预后较差（IgAN和FSGS均P < 0.05）。在多变量分析中，IL-10多态性仍然是进展的独立危险因素（Cox回归模型，IgAN和FSGS均P < 0.05）。