RT Journal Article
SR Electronic
T1 IL10 GGC Haplotype Is Positively and HLA-DQA1*05-DQB1*02 Is Negatively Associated with Radiographic Progression in Undifferentiated Arthritis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.090913
DO 10.3899/jrheum.090913
A1 Jennie Ursum
A1 Mignon A.C. van der Weijden
A1 Dirkjan van Schaardenburg
A1 Arend P.A. Prins
A1 Ben A.C. Dijkmans
A1 Jos W.R. Twisk
A1 Jakob B.A. Crusius
A1 Irene E. van der Horst-Bruinsma
YR 2010
UL http://www.jrheum.org/content/early/2010/05/12/jrheum.090913.abstract
AB 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.