Author:
URSUM JENNIE,van der WEIJDEN MIGNON A.C.,van SCHAARDENBURG DIRKJAN,PRINS AREND P.A.,DIJKMANS BEN A.C.,TWISK JOS W.R.,CRUSIUS JAKOB B.A.,van der HORST-BRUINSMA IRENE E.
Abstract
Objective.In rheumatoid arthritis (RA), many genetic markers, such as the shared-epitope (SE) alleles, are described in association with radiographic progression, but limited data are available on undifferentiated arthritis (UA). We investigated whether single-nucleotide polymorphisms (SNP) and haplotypes in immune response genes and HLA class II alleles are associated with radiographic progression in patients with early UA.Methods.Progression of radiographic damage was determined in white Dutch patients with early UA after 2 years of followup. Severe progression was defined as an increase in Sharp/van der Heijde Score ≥ 5 points after 2 years of followup. The remainder was classified as mild. These SNP were genotyped by Taqman technology: tumor necrosis factor (TNF) −1031, −863, −857, −308, −238; lymphotoxin-α (LTA) +368, +252; interleukin 10 (IL10) −2849, −1082, −819; IL1A −889, IL1B −31, +3953; and IL1RN +2018. Carriage of SE alleles and HLA-DQA1*05-DQB1*02 haplotype was established. These markers were analyzed in relation to radiographic progression.Results.Forty-eight out of 151 patients with early UA had severe radiographic progression. Severe radiographic progression was associated with an increased carrier frequency of SE alleles (OR 5.12, 95% CI 2.0–13.1, p < 0.001) and IL10 GGC haplotype (OR 2.8, 95% CI 1.4–5.8, p = 0.003). Mild radiographic progression was associated with the HLA-DQA1*05-DQB1*02 haplotype (OR 0.3, 95% CI, 0.1–0.8, p = 0.013) and with allele TNF −308A (OR 0.4, 95% CI, 0.2–0.9, p = 0.02).Conclusion.The SE and the IL10 GGC haplotype are associated with severe progression of radiographic damage, in contrast to the DQA1*05-DQB1*02 haplotype and the TNF −308A allele, which are associated with mild radiographic progression in early UA.
Publisher
The Journal of Rheumatology
Subject
Immunology,Immunology and Allergy,Rheumatology
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献