白细胞介素 2 受体 A（IL-2RA）和白细胞介素 2 受体 B（IL-2RB）基因与早期类风湿关节炎患者侵蚀状态的相关性（ESPOIR 和 RMP 队列研究）。
Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts).
机构信息
INSERM, UMR1027, 31062 Toulouse cedex 9, France; Université de Toulouse III, UMR1027, 31062 Toulouse cedex 9, France; Rheumatology Center, Purpan Teaching Hospital, CHU Toulouse, 1 place du Dr-Baylac, 31059 Toulouse cedex 9, France.
Rheumatology Department, Lapeyronie Teaching Hospital, 34295 Montpellier cedex 5, France.
出版信息
Joint Bone Spine. 2014 May;81(3):228-34. doi: 10.1016/j.jbspin.2013.10.002. Epub 2013 Nov 5.
OBJECTIVES
To assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.
METHODS
This work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.
RESULTS
The AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14-3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68-6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94-18.69], p = 0.002) on the risk of erosions in ACPA+ patients.
CONCLUSION
A haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.
目的
评估白细胞介素 2 受体 A（IL-2RA）（rs2104286）和白细胞介素 2 受体 B（IL-2RB）（rs743777 和 rs3218253）基因中的单核苷酸多态性（SNPs）对类风湿关节炎（RA）患者侵蚀风险的影响。
方法
本研究来源于两个早期 RA 的前瞻性队列：ESPOIR（n=439）和 RMP（n=180）。根据 IL2RA（rs2104286）的基因型或 IL2RB 的 2 个 SNPs 构建的单体型，比较基线和 1 年时患者的侵蚀比例。采用 Mantel-Haenszel 法对 IL-2RB 两个 SNPs 的单体型对侵蚀风险的影响进行荟萃分析。采用多变量模型评估 IL-2RB 单体型对侵蚀风险的独立影响。
结果
IL-2RB 的 AC 单体型与 ESPOIR 队列中 ACPA 阳性患者的侵蚀率显著相关（侵蚀率：AC/AC：78% vs. GC 或 GT/GC 或 GT：44%，p=0.001）。ESPOIR 和 RMP 队列的荟萃分析证实，在整个样本中，AC 单体型的携带与 1 年时的侵蚀率显著相关（OR[95%CI] = 1.92[1.14-3.22]，p=0.01）和 ACPA 阳性患者（OR[95%CI] = 3.34[1.68-6.67]，p=0.0006）。ESPOIR 队列的多变量模型显示，AC 单体型的携带对 ACPA+患者的侵蚀风险有独立影响（6.03[1.94-18.69]，p=0.002）。
结论
位于 IL-2RB 基因上的 2 个 SNPs 构建的单体型与早期 RA 的侵蚀状态相关。
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