Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis.
Publication/Presentation Date
12-1-2008
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.
Volume
58
Issue
12
First Page
3941
Last Page
3950
ISSN
0004-3591
Published In/Presented At
Mamyrova, G., O'Hanlon, T. P., Sillers, L., Malley, K., James-Newton, L., Parks, C. G., Cooper, G. S., Pandey, J. P., Miller, F. W., Rider, L. G., & Childhood Myositis Heterogeneity Collaborative Study Group (2008). Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis. Arthritis and rheumatism, 58(12), 3941–3950. https://doi.org/10.1002/art.24039
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
19035492
Department(s)
Department of Pediatrics
Document Type
Article