Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis.
OBJECTIVE
To test if interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in rheumatoid arthritis (RA).


METHODS
The study included 108 patients with early RA followed up for 2 years and 128 healthy controls. From genomic DNA, 6 polymorphisms in genes for IL-1beta, IL-1Ra, IL-10, and IL-4 were typed. Allelic frequencies and carriage rates were compared between RA patients and controls, between patients with erosive and nonerosive RA, and between patients with or without sustained remission.


RESULTS
The RP1 allele of the IL-4 gene was found with a significantly higher frequency in RA patients compared with controls. The combination of an RA-related HLA-DR allele expressing shared epitope and the presence of allele E2 in IL-1beta exon 5 was found to expose patients to an increased risk of erosive disease, with an odds ratio of 8.20 (95% confidence interval 2.59-25.84, P < 0.0001). No significant association was observed between polymorphisms and the occurrence of sustained remission.


CONCLUSIONS
This report, for the first time, indicates an association between RA and a polymorphic IL-4 gene sequence located in 5q31-33. In addition, the results show the prognostic value of a polymorphism in IL-1beta exon 5, which allowed prediction of erosive disease with a specificity of 91.8% in 42.1% of patients. Although these observations are very interesting, they have to be considered preliminary and will need to be confirmed.
Cantagrel
A
A
Service de Rhumatologie, Hôpital Rangueil, Toulouse, France.
Navaux
F
F
Loubet-Lescoulié
P
P
Nourhashemi
F
F
Enault
G
G
Abbal
M
M
Constantin
A
A
Laroche
M
M
Mazières
B
B
D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D004198:Disease Susceptibility; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000235:genetics*
D017931:DNA Primers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D016753:Interleukin-10; D015847:Interleukin-4; D004247:DNA