Association of interleukin-6 and interleukin-10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody status
Association of interleukin-6 and interleukin-10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody status
复制标题
DOI：
10.1002/art.22814
复制
发表时间：
2007-08-01
影响因子：
--
通讯作者：
Wilson, A. G.
中科院分区：
文献类型：
--
作者：
Marinou, I.;Healy, J.;Wilson, A. G.
目标。最近的证据强调了类风湿关节炎（RA）放射学损伤的主要遗传因素。本研究的目的是确定白介素-1 （IL-1）、IL-6、IL-10、蛋白酪氨酸磷酸酶N22 （PTPN22）和硒蛋白S位点的遗传变异是否与放射学损伤有关。在RA患者的横断面人群（n = 964）中确定了改良的Larsen放射学损伤评分。同时检测类风湿因子（RF）和抗环瓜氨酸肽（anti-CCP）。采用Kruskal-Wallis非参数检验比较各基因型组的放射学损伤中位数评分，然后采用Cuzick非参数检验趋势来评估基因剂量效应。IL-6 -174G等位基因剂量与放射学损伤增加存在相关性（P = 0.005），但仅适用于RIF阳性（P = 0.004）或抗ccp阳性（P = 0.01）的患者。IL-10 -592CC基因型患者比AC或AA基因型患者有更广泛的放射学损伤（P = 0.006），但这仅在RF阴性（P = 0.002）或抗ccp阴性（P = 0.002）的患者中观察到。然而，RIF状态和抗ccp状态与IL-6或IL-10基因型无关。除了PTPN22 +1858T与放射学损伤增加的边缘关联外，未发现其他遗传关联。据报道，IL-6 - 174G与高IL-6产生有关，IL-10 - 592与低IL-10产生有关，我们自己的结果支持遗传决定的细胞因子产生失调在疾病严重程度中的作用。这些基因型与RF和抗ccp抗体状态缺乏关联，表明它们作用于自身抗体产生的下游。我们得出结论，IL-6和IL-10基因型可能分别用于预测自身抗体阳性和自身抗体阴性患者的疾病严重程度。
Objective. Recent evidence has highlighted a major genetic contribution to radiographic damage in rheumatoid arthritis (RA). The objective of this study was to determine whether genetic variants in the loci for interleukin-1 (IL-1), IL-6, IL-10, protein tyrosine phosphatase N22 (PTPN22), and selenoprotein S are associated with radiographic damage.Methods. Modified Larsen scores of radiographic damage were determined in a cross-sectional population of patients with RA (n = 964). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were also assayed. The Kruskal-Wallis nonparametric test was used to compare median radiographic damage scores across genotype groups, followed by the Cuzick nonparametric test for trend to assess gene-dose effects.Results. An allele-dose association of IL-6 -174G with increasing radiographic damage was present (P = 0.005), but only in patients who were RIF positive (P = 0.004) or anti-CCP positive (P = 0.01). Patients with the IL-10 -592CC genotype had more extensive radiographic damage than did those with the AC or AA genotype (P = 0.006), but this was observed only among patients who were RF negative (P = 0.002) or anti-CCP negative (P = 0.002). However, RIF status and anti-CCP status were not associated with the IL-6 or IL-10 genotype. No other genetic associations were detected, apart from a marginal association of PTPN22 +1858T with increased radiographic damage.Conclusion. The reported associations of IL-6 - 174G with high IL-6 production and IL-10 - 592 with low IL-10 production and our own results support a role of genetically determined dysregulated cytokine production in disease severity. The lack of association of these genotypes with RF and anti-CCP antibody status suggests that they act downstream of autoantibody production. We conclude that IL-6 and IL-10 genotypes may be useful in predicting disease severity in autoantibody-positive and autoantibody-negative patients, respectively.