Gene polymorphisms and pharmacogenetics in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient's genetic profile.

Keywords: IL-1; Pharmacogenomic; TNF; cytokines; gene polymorphisms.; rheumatoid arthritis.

Fig. (1)

Schematic representation of the tumor necrosis factor-α (TNF-α) gene, showing some of the most relevant single nucleotide polymorphisms (SNPs). The horizontal arrows in the middle row indicate the transcriptional orientation of the TNF and lymphotoxin (LT) genes. Diagonally highlighted regions in exons 1 and 4 indicate the untranslated regions (UTRs).

Fig. (2)

Molecular mechanism of biologic therapies: A) The tumor necrosis factor-α (TNF-α) blocker, Etanercept. B) The tumor necrosis factor-α (TNF-α) blocker, Infliximab. C) The tumor necrosis factor-α (TNF-α) blocker, Adalimumab. D) The interleukin-1 (IL-1) blocker, Anakinra, a recombinant form of the human IL-1 receptor antagonist (IL-1RA).