Association of TNF-alpha polymorphism (-308 A/G) with high activity of rheumatoid arthritis and therapy response to etanercept

Abstract

Introduction. Genetic markers are significant predictive factors in the assessment of therapeutic response of rheumatoid arthritis (RA) to biological medication. Objective. The aim of the study was to determinate the association of TNF-? -308 G/A polymorphism with a high RA activity and its predictive value in therapeutic response after 12 months of treatment with Etanercept. Methods. The study enrolled 132 patients with RA treated with Methotrexate (MTX) and 58 control subjects. The -308 TNF polymorphism was examined using the polymerase chain reaction - restriction fragment length polymorphism (PCR- RFLP). The patients were divided into two groups: group A with A/A and A/G genotype and group G with G/G genotype. After 12 months, beside MTX, Etanercept was introduced in 36 patients. We compared clinical activity among the groups at the beginning and after one year of therapy by using DAS28 SE (Disease activity score with sedimentation). Results. There was no significant difference found in the distribution of G and A allele in the RA group compared to the control group. A significantly higher disease activity was noticed in A compared to the G group (DAS28 SE: 6.31 to 5.81; p<0.05). The patients with A allele kept the majority of the disease activity even after a year of study (DAS28 SE: 5.25 to 3.89). After a year of MTX and Etanercept therapy, a significantly larger proportion of patients in the G group displayed a good clinical response to treatment compared to the A group (81.5% to 25%; p<0.05). The average change of DAS28 SE in G group was 2.24, while in the A group DAS 28 reduction was significantly lower (1.17; p=0.005). Conclusion. There was no significant difference in the frequency of A in the patients with RA compared to healthy subjects. The presence of A allele is associated with more serious clinical presentation of the disease and lower therapeutic response to Etanercept.