Evaluating the Role of IL-6-174 G/C (rs1800795) Gene Polymorphism in Modulating Serum Levels of Some Inflammatory Biomarker and Therapeutic Outcomes with Rituximab in Iraqi Rheumatoid Arthritis Patients

Abstract

Rituximab is a chimeric monoclonal antibody used in the treatment of rheumatoid arthritis (RA). However, patients receiving it show various degrees of responsiveness without knowing the exact causes behind this diversity. Interleukin-6, among other inflammatory biomarkers, is involved in RA pathogenicity. This study investigated the role of IL-6-174 G/C (rs1800795) gene polymorphism at the promoter region and its possible effect on serum level of different inflammatory biomarkers and response to Rituximab (RTX) among RA patients, and whether this genotyping can aid clinicians in choosing eligible patients for RTX. Ninety adult RA patients from the Rheumatology Unit of Baghdad Teaching Hospital were recruited for this cross-sectional study. All were receiving RTX intravenously. Blood samples were taken from them for genetic analysis and measuring serum levels of IL-1 beta, IL-6, TNF-, and their effect on Rituximab response, which was measured using disease activity score in 28 joints (DAS 28 score). From the pooled sample of 90 patients, 50 of them were RTX responders, and 40 of them were RTX non-responders. Regarding the studied SNP, no significant difference was obtained between the expected and observed proportion of rs1800795 C>G (P-value=0.378). The proportion of patients with G allele was significantly higher in the RTX responders (73%) compared to RTX non-responders (45%) (P-value<0.001). IL-6 level was significantly higher in the CC phenotype (48.06 ±23.53) compared to the GC phenotype (36.97 ±19.57) and GG phenotype (26.48 ±18) (P-value=<0.001). As conclusion for optimizing RTX treatment among RA patients, the genotyping study of the promoter region of IL-6 could be a valuable marker, different allelic at rs1800795 affected the serum levels of different inflammatory biomarkers and extended to affect RTX response showing that GG presence reflected a better response to RTX treatment than GC and CC genotypes.