Polymorphism at position +896 of the toll-like receptor 4 gene interferes with rapid response to treatment in rheumatoid arthritis.
The aim of this study was to determine whether the +896 A-->G substitution of the Toll-like receptor 4 (TLR4) gene, causing the Asp299-->Gly change in the extracellular domain of TLR4, influences treatment response in recent-onset rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were treated either with only one disease-modifying antirheumatic drug (DMARD) with or without prednisolone (single group), or with three DMARDs and prednisolone (combination group). Patients homozygotic for the wild-type +896A allele were compared with those having the polymorphic G allele in terms of early clinical response (at 6 months) by the 28-joint Disease Activity Score (DAS28). 1 of 20 (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with TLR4 +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in remission (p = 0.001). DAS28 of the single group with TLR4 +896AG or GG was higher than with AA (p = 0.019). In the combination group, remission rates and DAS28 values were comparable between the genotypes. The polymorphic TLR4 +896G allele may impair treatment response to single DMARD treatment in recent-onset rheumatoid arthritis.
Kuuliala
K
K
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, PO Box 21 (Haartmaninkatu 3), FIN-00014 Helsinki, Finland. krista.anttonen@helsinki.fi
Orpana
A
A
Leirisalo-Repo
M
M
Kautiainen
H
H
Hurme
M
M
Hannonen
P
P
Korpela
M
M
Möttönen
T
T
Paimela
L
L
Puolakka
K
K
Karjalainen
A
A
Repo
H
H
D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic; D011239:Prednisolone / Q000627:therapeutic use; D011379:Prognosis; D012720:Severity of Illness Index; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D005938:Glucocorticoids; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D011239:Prednisolone