Genetic influences modulating the radiological severity of rheumatoid arthritis.

This review focuses on the contribution of genetic markers to the severity of radiological damage in rheumatoid arthritis (RA). Currently available biomarkers of more severe disease include elevated erythrocyte sedimentation rates or C-reactive protein levels and rheumatoid factor (RF) or anticyclic citrullinated protein antibodies positivity; however, these biomarkers explain a relatively modest proportion of the variance in radiological damage. An important role of genetic factors on RA severity has recently emerged but studies to date have generally been of low statistical power and many have not been replicated. Genetic markers have a number of advantages over conventional biomarkers; genotypes are stable, measurable at disease onset, remain unchanged by treatment and are amenable to high-throughput assays. The recent advances in genome-wide genetic analysis should lead to a more comprehensive understanding of RA severity genes. This knowledge could be used, along with existing biomarkers, to therapeutically target subjects at risk of poor radiological outcome.