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


CONCLUSIONS
TNFalpha and IL-1 genetic polymorphisms contribute to the development of juvenile DM and may also be indicators of disease severity.
Mamyrova
Gulnara
G
National Institute of Environmental Health Sciences, NIH, Bethesda, Maryland 20892-1301, USA.
O'Hanlon
Terrance P
TP
Sillers
Laura
L
Malley
Karen
K
James-Newton
Laura
L
Parks
Christina G
CG
Cooper
Glinda S
GS
Pandey
Janardan P
JP
Miller
Frederick W
FW
Rider
Lisa G
LG
D002648:Child; D002675:Child, Preschool; D003882:Dermatomyositis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha