Predictive value of interleukin 1 gene polymorphisms for surgery

OBJECTIVES: To determine the influence of interleukin 1alpha (IL1alpha), IL1beta, and IL1 receptor antagonist gene polymorphisms on disease outcome as assessed by the need for major joint surgery within 15 years of diagnosis.

PATIENTS AND METHODS: 50 patients with rheumatoid arthritis (RA) who required major joint surgery (hip, knee, or shoulder arthroplasty) within a 15 year period of disease diagnosis and 50 patients with RA with disease duration greater than 15 years and no major surgery were recruited together with 66 normal west of Scotland controls. Genomic DNA and polymerase chain reaction were used to determine polymorphisms in the genes for IL1alpha, IL1beta, and IL1 receptor antagonist. For all patients with RA recruited to the study, HLA-DR beta1 gene status was recorded as was the erythrocyte sedimentation rate (ESR) at the first ever clinic visit.

RESULTS: No difference in the allele frequencies or genotypes of the IL1alpha and IL1 receptor antagonist gene polymorphisms was found between the controls and patients with RA, with or without previous surgery. IL1beta allele 2 was overrepresented in patients with RA who had undergone surgery compared with patients who had not (40% v 27%, chi(2)=4, 1df, p=0.04). ESR at the first ever clinic visit was significantly higher in those carrying allele 2 (36 mm/1st h v 22 mm/1st h, p=0.04). When patients, with or without previous surgery, who did not carry two disease associated HLA-DR beta1 alleles were compared, an increase in allele 2 was observed in the surgery cohort (42% v 25%, chi(2)=4.8, 1df, p=0.03).

CONCLUSIONS: Patients who require major joint surgery were found to carry the IL1beta allele 2 more often than expected. Patients with this allele also had a higher initial ESR. This may be useful in predicting early surgery in patients who do not carry two disease associated HLA-DR beta1 alleles. Although these findings are interesting, further functional and epidemiological studies to confirm these observations are required.