1. Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis
- Author
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Gulnara, Mamyrova, 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, and Lawrence S, Zemel
- Subjects
Male ,Linkage disequilibrium ,Genotype ,Immunology ,Interleukin-1beta ,Severity of Illness Index ,Dermatomyositis ,Linkage Disequilibrium ,Rheumatology ,Risk Factors ,Immunopathology ,Interleukin-1alpha ,Severity of illness ,medicine ,Immunology and Allergy ,Humans ,Pharmacology (medical) ,Allele ,Child ,Juvenile dermatomyositis ,Polymorphism, Genetic ,business.industry ,Tumor Necrosis Factor-alpha ,Odds ratio ,HLA-DR Antigens ,medicine.disease ,Child, Preschool ,Female ,business ,HLA-DRB1 Chains - Abstract
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).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.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.TNFalpha and IL-1 genetic polymorphisms contribute to the development of juvenile DM and may also be indicators of disease severity.
- Published
- 2008