Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis
Arthritis and Rheumatism
Objective. To study tumor necrosis factor α (TNFα) and interleukin-1 (IL-1) cytokine polymorphisms as possible risk and protective factors, define their relative importance, and examine these as severity factors in patients with juvenile dermatomyositis (DM). Methods. TNFα and IL-1 cytokine polymorphism and HLA typing were performed in 221 Caucasian patients with juvenile DM, and the results were compared with those in 203 ethnically matched healthy volunteers. Results. The genotypes TNFα -308AG (odds ratio [OR] 3.6), TNFα -238GG (OR 3.5), and IL-1α -4845TT (OR 2.2) were risk factors, and TNFα -308GG (OR 0.26) as well as TNFα -238AG (OR 0.22) were protective, for the development of juvenile DM. Carriage of a single copy of the TNFα -308A (OR 3.8) or IL-1β +3953T (OR 1.7) allele was a risk factor, and the TNFα -238A (OR 0.29) and IL-1α +4845G (OR 0.46) alleles were protective, for juvenile DM. Random Forests classification analysis showed HLA-DRB1*03 and TNFα -308A to have the highest relative importance as risk factors for juvenile DM compared with the other alleles (Gini scores 100% and 90.7%, respectively). TNFα -308AA (OR 7.3) was a risk factor, and carriage of the TNFα -308G (OR 0.14) and IL-1α -889T (OR 0.41) alleles was protective, for the development of calcinosis. TNFα -308AA (OR 7.0) was a possible risk factor, and carriage of the TNFα -308G allele (OR 0.14) was protective, for the development of ulcerations. None of the studied TNFα, IL-1α, and IL-1β polymorphisms were associated with the disease course, disease severity at the time of diagnosis, or the patient's sex. Conclusion. TNFα and IL-1 genetic polymorphisms contribute to the development of juvenile DM and may also be indicators of disease severity. © 2008, American College of Rheumatology.
Mamyrova, G., O'Hanlon, T., Sillers, L., Malley, K., James-Newton, L., Parks, C., Cooper, G., Pandey, J., Miller, F., & Rider, L. (2008). Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis. Arthritis and Rheumatism, 58 (12). http://dx.doi.org/10.1002/art.24039