Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis

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


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Child
  • Child, Preschool
  • Dermatomyositis / epidemiology*
  • Dermatomyositis / genetics*
  • Female
  • Genotype
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Interleukin-1alpha / genetics*
  • Interleukin-1beta / genetics*
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Genetic
  • Risk Factors
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / genetics*


  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Interleukin-1alpha
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha