Association between genetic polymorphism in tumor necrosis factor-alpha gene and adverse effects of etanercept in rheumatoid arthritis patients

Abstract

Background. Gene polymorphisms affect etanercept’s pharmacokinetics, pharmacodynamics, and side effects. This effect is evidenced by the extensive genetic variation in the drug’s targets. Objectives. This study aims to find the association between different genotypes of the promoter region of the TNF-α gene at -308G/A(rs1800629), -857C/T(rs1799724), -863 C/A(rs1800630), -1031 T/C (rs1799964), -806 C/T (rs4248158) and -376 G/A (rs1800750) and the side effects of ETN that occurred to Iraqi RA patients. Method. The trial included patients with rheumatoid arthritis who had been using ETN for at least six months. The participants were from the Baghdad Teaching Hospital Rheumatology Unit. The PCR was sequenced to determine the polymorphism in the TNF- promoter region at sites -308 G/A (rs1800629), -857 C/T (rs1799724), -863 C/A (rs1800630), -1031 T/C (rs1799964), and -376 G/A (rs4248158) (rs1800750). The link between the genetic variation at these loci and the etanercept’s most frequent adverse effect was then investigated. Results. The only genotype of (-376 G/A) significantly related to an increased risk of upper respiratory tract infection is the GG genotype, according to the results of this study. However, genotypes for the remaining SNPs did not demonstrate a statistically significant association between ETN and an increased risk of upper respiratory tract infections, injection site response, or skin rash in patients. Conclusion. This study revealed that only the GG genotype of (-376 G/A) was significantly associated with an elevated risk of upper respiratory tract infection.

Keywords

• adverse effects
• etanercept
• rheumatoid arthritis
• genetic polymorphism
• tnf-α