Although a common, non-synonymous variant in the IL-6 receptor gene (IL6Rrs2228145" genes_norm="3570">Asp358Ala; rs2228145 A>C) is associated with the risk of several common diseases, with the 358Ala allele conferring protection from coronary heart disease (CHD), rheumatoid arthritis (RA), atrial fibrillation (AF), abdominal aortic aneurysm (AAA), and increased susceptibility to asthma, the variant's effect on IL-6 signaling is not known.
Gene expression studies showed that blockade of the interleukin-6 receptor (IL-6R) gene (IL6R) using TCZ induced a significant decrease in the expression of numerous chemokine and T cell activation genes in the RA synovium.
Multiple studies have shown seemingly unfavorable changes in lipid profiles associated with interleukin-6 receptor (IL-6R) antagonists and some other therapies for rheumatoid arthritis.
Soluble interleukin-6 receptor in plasma and in lymphocyte culture supernatants of healthy individuals and patients with systemic lupus erythematosus and rheumatoid arthritis.
The recent meta-analysis of GWAS has expanded the total number of RA-associated loci to more than 100, out of which approximately ∼97% (98 variants) loci are located in non-coding regions, and the other ∼3% (3 variants) are in three different non-HLA genes, i.e., TYK2 (Prp1104Ala), IL6R (Asp358Ala), and PTPN22 (Trp620Arg).
This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials.