Ms Balding and Dr. Kane contributed equally to this work.
Cytokine gene polymorphisms: Association with psoriatic arthritis susceptibility and severity
Article first published online: 6 MAY 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 5, pages 1408–1413, May 2003
How to Cite
Balding, J., Kane, D., Livingstone, W., Mynett-Johnson, L., Bresnihan, B., Smith, O. and FitzGerald, O. (2003), Cytokine gene polymorphisms: Association with psoriatic arthritis susceptibility and severity. Arthritis & Rheumatism, 48: 1408–1413. doi: 10.1002/art.10935
- Issue published online: 6 MAY 2003
- Article first published online: 6 MAY 2003
- Manuscript Accepted: 14 JAN 2003
- Manuscript Received: 19 DEC 2002
- Novo Nordisk
- The Health Research Board of Ireland
To determine whether functional cytokine gene polymorphisms influence disease susceptibility and phenotype in patients with psoriatic arthritis (PsA).
DNA was obtained from 147 PsA patients and 389 controls. Seven functional proinflammatory (interleukin-1β [IL-1β] +3953, IL-6 −174, tumor necrosis factor α [TNFα] −308, TNFβ +252) and antiinflammatory (IL-10 −1082, IL-10 −592, IL-1 receptor antagonist [intron 2, 86 bp, variable-number tandem repeat]) gene polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism assays.
No significant difference in genotype frequencies was observed between the control and the PsA patient populations, and no association with Steinbrocker functional class, disease classification (polyarticular or oligoarticular), presence of spinal involvement, or age at PsA onset was observed. The presence of joint erosions was significantly associated with the TNFα −308 and TNFβ +252 polymorphisms (P < 0.0001 and P = 0.0017, respectively). Frequencies of the TNFα −308 and TNFβ +252 genotypes were also significantly different (P = 0.0078 and P = 0.0486, respectively) in a group of progressors (patients with early PsA in whom the number of joint erosions in the hands and feet increased over a median interval of 24 months) compared with a group of nonprogressors. Age at psoriasis onset was significantly associated with the TNFβ +252 and TNFα −308 polymorphisms (P = 0.0003 and P = 0.0081, respectively). The TNFB2B2 and TNFα −308 AA genotypes were associated with the earliest mean ages at psoriasis onset.
The TNFα −308 and TNFβ +252 polymorphisms were significantly associated with age at psoriasis onset, presence of joint erosions in PsA, and progression of joint erosions in early PsA. TNF gene polymorphisms may be useful prognostic markers in PsA, and these results support the rationale for using anti-TNF treatment in patients with severe, progressive PsA.