白介素-10基因多态性与狼疮性肾炎的关系

Interleukin-10 gene polymorphism in patients with lupus nephritis

目的 :探讨白介素 10 (IL 10 )基因多态性与狼疮性肾炎 (LN)的发病和临床病理损害的联系及其在LN分子诊断中的意义。 方法 :提取 10 0例健康志愿者及 2 4 6例LN患者全血DNA ,限制性片断长度多态性法检测IL 10基因 5 92位点A/C单核苷酸多态性在正常人群和LN患者总体及不同病理亚型组的分布 ,比较不同基因型组的临床表现、病理损害的差异 ,并研究其对血清IL 10水平的影响。 结果 :IL 10基因 5 92A/C多态性在正常人群和LN患者的分布无显著差别 ,IL 10高表达基因型AC&CC患者的疾病活动性指数、尿蛋白、尿沉渣红细胞和肾小球袢内血栓的发生率均显著高于IL 10低表达基因型AA患者 ;结合肾活检病理分型进行分析发现 ,IL 10高表达相关的基因型 (AC&CC)在Ⅳ型LN患者的分布显著高于Ⅱ型和Ⅴa型患者。LN患者各基因型组血清IL 10水平无统计学差异 ,但AA型 <AC型 <CC型逐渐增高的趋势。 结论 :IL 10基因 5 92位点多态性不仅与LN疾病活动性相关 ,还对临床和免疫病理损害产生影响。携带IL 10高表达相关C等位基因的患者 ,肾小球弥漫增殖损害的发生率明显增高 ,表明个体IL

Objective:To investigate the relationship between the gene polymorphism of interleukin-10 (IL-10), and the pathogenesis of lupus nephritis(LN) and clinico-pathological characteristics in patients with LN,and to assess its role in the molecular diagnosis of LN. Methodology:DNA was extracted from 100 healthy volunteers and 246 patients with LN. PCR-RFLP was used to detect -592 A/C polymorphism in IL-10 gene promoter. The distribution of IL-10 genotypes was compared between healthy controls and LN patients to evaluate the relation of IL-10 with the susceptibility to LN, and among patients with LN-Ⅳ, Ⅴa, Ⅴb and Ⅱ to assess the role of IL-10 in diversified immuno-pathological lesions in LN. The clinico-pathological characteristics of LN patients with different IL-10 genotypes were analyzed. Serum IL-10 level of patients with different IL-10 genotypes was detected by ELISA method. Results:No significant difference was found in the distribution of IL-10 gene polymorphism between healthy controls and patients with LN. Patients with genotypes carrying allele C had higher DAI, severe proteinuria and hematuria, and higher frequency of glomerular thrombi than those with genotype AA. Patients with LN-Ⅳ had higher frequency of genotypes AC and CC, related to higher IL-10 production, than those with LN-Ⅱ and Ⅴa. The serum level of IL-10 in patients with three genotypes displayed a tendency of CC > AC > AA, which did not reach a statistical significance. Conclusion:The -592 A/C polymorphism in IL-10 gene was related to disease activity of SLE, and clinico-pathological injury of LN. Patients with genotypes carrying allele C, related to more IL-10 production, had higher risk of diffuse proliferative lesion. Our data indicate that the individual differences in responsiveness to IL-10 may influence the clinico-pathological characteristics of LN.