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Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis. Arthritis Rheum 2008 Dec;58(12):3941-50

Date

11/28/2008

Pubmed ID

19035492

Pubmed Central ID

PMC2674642

DOI

10.1002/art.24039

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.

Author List

Mamyrova G, O'Hanlon TP, Sillers L, Malley K, James-Newton L, Parks CG, Cooper GS, Pandey JP, Miller FW, Rider LG, Childhood Myositis Heterogeneity Collaborative Study Group

Author

Judyann C. Olson MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Child
Child, Preschool
Dermatomyositis
Female
Genotype
HLA-DR Antigens
HLA-DRB1 Chains
Humans
Interleukin-1alpha
Interleukin-1beta
Linkage Disequilibrium
Male
Polymorphism, Genetic
Risk Factors
Severity of Illness Index
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280