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Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis. Mamyrova G et al. Arthritis Rheum. (2008)

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

Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis.

Collaborators (158)

Abramson LS, Adams BS, Adams EM, Alepa FP, Amoroso K, Arioglu E, Arnett FC, Arthur E, Athreya BH, Baer AN, Ballinger SH, Barron KS, Bingham AC, Blocker WP, Bohn J, Bohnsack JF, Boire G, Borzy MS, Botstein GR, Bowyer SL, Brackett RW, Brooks EB, Brunet C, Bunch T, Cartwright VW, Cawkwell GD, Chanock SJ, Chao CP, Crisp D, Cron RQ, Culp R, Daigh J, David L, Delafield FC, Eggert JF, Eichenfield AH, Elder M, Ellman J, Ellsworth JE, Etheridge C, Evans S, Fearn K, Finkel TH, Foster CB, Fuhlbrigge RC, Garwood VF, Gedalia A, Gehringer N, George SW, Gewanter HL, Goldmuntz EA, Goldsmith DP, Gordon GV, Greenbaum LM, Gross KR, Haftel H, Hawkins-Holt M, Hendrics C, Henrickson M, Higgins GC, Hollister JR, Hopp R, Hudson B, Huh E, Ilowite NT, Imundo LF, Jacobs JC, Jerath RS, Johnson CR, Jones M, Jones O, Jung LK, Kagen LJ, Kahn SJ, Kantor TG, Katona IM, Keenan GF, Keystone EC, Kimura Y, Kingsbury DJ, Klein SJ, Knee CM, Koenig J, Lang BA, Lasky A, Lawton A, Levine J, Lindsley CB, Lipnick RN, Lourie SH, Love E, Lundberg MS, Madson KL, Malleson PN, Maneice D, Mariano A, Marks H, Martin AL, Matthew F, Miller J, Mitchell SR, Moallem HJ, Morel PA, Morishima C, Murphy FT, Nathan H, Neumeyer A, Oddis CV, Olson JC, Onel K, Ostrov BE, Pachman LM, Pappu R, Passo MH, Perez MD, Person DA, Peterson KS, Plotz PH, Punaro MG, Radis CD, Ray LI, Rennebohm RM, Reuman PD, Reveille JD, Rivas-Chacon RF, Rosenberg AL, Rothman D, Schlesinger PA, Schuberth KC, Scott DW, Seamon D, Shaham B, Sheets RM, Sherry DD, Sinal SH, Stafford FJ, Stang H, Sundel RP, Szer IS, Targoff IN, Taylor S, Taylor-Albert ES, Thomas DE, Vehe RK, Villalba ML, Vogelgesang SA, Vogler LB, Von Scheven E, Wahl S, Wallace CA, Wander HJ, Weinstein A, Wells J, White PH, Wright GC, Yee J, Yung CM, Zemel LS.

Author information

1
National Institute of Environmental Health Sciences, NIH, Bethesda, Maryland 20892-1301, USA.

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.

PMID:
19035492
PMCID:
PMC2674642
DOI:
10.1002/art.24039
[Indexed for MEDLINE]
Free PMC Article
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