IL10 GGC haplotype is positively and HLA-DQA1*05-DQB1*02 is negatively associated with radiographic progression in undifferentiated arthritis.
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 > or = 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-alpha (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).


CONCLUSIONS
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.
Ursum
Jennie
J
VU University Medical Centre, Department of Rheumatology, 1007 MB Amsterdam, The Netherlands.
van der Weijden
Mignon A C
MA
van Schaardenburg
Dirkjan
D
Prins
Arend P A
AP
Dijkmans
Ben A C
BA
Twisk
Jos W R
JW
Crusius
Jakob B A
JB
van der Horst-Bruinsma
Irene E
IE
D000328:Adult; D000368:Aged; D001168:Arthritis / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology*; D059848:HLA-DQ alpha-Chains; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10