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. 2008 Dec;58(12):3941-50.
doi: 10.1002/art.24039.

Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis

Gulnara Mamyrova  1 , Terrance P O'Hanlon, Laura Sillers, Karen Malley, Laura James-Newton, Christina G Parks, Glinda S Cooper, Janardan P Pandey, Frederick W Miller, Lisa G Rider; Childhood Myositis Heterogeneity Collaborative Study Group
Collaborators, Affiliations

Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis

Gulnara Mamyrova et al. Arthritis Rheum. 2008 Dec.

Abstract

Objective: To study tumor necrosis factor alpha (TNFalpha) 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: TNFalpha 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 TNFalpha -308AG (odds ratio [OR] 3.6), TNFalpha -238GG (OR 3.5), and IL-1alpha +4845TT (OR 2.2) were risk factors, and TNFalpha -308GG (OR 0.26) as well as TNFalpha -238AG (OR 0.22) were protective, for the development of juvenile DM. Carriage of a single copy of the TNFalpha -308A (OR 3.8) or IL-1beta +3953T (OR 1.7) allele was a risk factor, and the TNFalpha -238A (OR 0.29) and IL-1alpha +4845G (OR 0.46) alleles were protective, for juvenile DM. Random Forests classification analysis showed HLA-DRB1*03 and TNFalpha -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). TNFalpha -308AA (OR 7.3) was a risk factor, and carriage of the TNFalpha -308G (OR 0.14) and IL-1alpha -889T (OR 0.41) alleles was protective, for the development of calcinosis. TNFalpha -308AA (OR 7.0) was a possible risk factor, and carriage of the TNFalpha -308G allele (OR 0.14) was protective, for the development of ulcerations. None of the studied TNFalpha, IL-1alpha, and IL-1beta polymorphisms were associated with the disease course, disease severity at the time of diagnosis, or the patient's sex.

Conclusion: TNFalpha and IL-1 genetic polymorphisms contribute to the development of juvenile DM and may also be indicators of disease severity.

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