Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA)
are chronic and systemic diseases with an important inflammatory component and differing
manifestations, all causing a significant decline in the quality of life of patients. RA produces
bone and cartilage destruction, as well as a wide variety of extra-articular manifestations; AS
mainly affects joints in the spine and sacroilium in the pelvis, and can cause eventual fusion of
the spine; and PsA is an inflammatory arthritis associated with psoriasis.
These diseases are characterized by an unknown aetiology as well as a strong genetic
contribution, supported by evidence from family and twin studies, linkage studies and
population-based association studies. Proinflammatory cytokines, such as tumour necrosis
factor-α (TNF-α) and several interleukins (IL-1, IL-6, IL-12) mediate the pathogeneses of
these diseases. The human leukocyte antigen (HLA) region has been consistently associated
with autoimmune pathologies, with HLA-DR mainly associated with RA and HLA-B27 with
both AS and PsA.
These chronic inflammatory diseases are highly heterogeneous in all their aspects, including
drug efficacy and toxicity in individual patients. A substantial proportion of patients do not
respond efficiently to classical therapies and/or experience toxicity limiting further treatment,
both of which lead to progression of inflammation. This high inter-individual variability in
drug response and toxicity gives rise to the need to individualize and optimize therapy with
anti-rheumatic agents, such as DMARDs [i.e., Methotrexate (MTX) and biological agents (i.e.,
anti-TNF agents)]. Studies in the field of pharmacogenetics are necessary to identify potential
markers associated with clinical response. To date, many polymorphisms in genes associated
not only with the diseases, but also with drug-metabolizing enzymes, drug targets and
transporters, have been analysed, showing in some cases conflicting results. The aim of this
review is to describe the state of the art of pharmacogenetics in three important chronic
inflammatory diseases, RA, AS and PsA.
Keywords: Genetics, pharmacogenetics, inflammatory disease, rheumatoid
arthritis, psoriatic arthritis, ankylosing spondylitis.
