Genetic aspects of rheumatic diseases

Abstract

In this review on the genetic aspects of rheumatic diseases, the approach was taken (i) to discuss, in general, important principles in the identification of susceptibility genes and (ii) to focus on five autoimmune rheumatic diseases that have the characteristics of complex diseases and in which important advances have been made in the identification of the genetic component. A decade ago, most reviews on the genetics of rheumatic diseases focused almost exclusively on a discussion of the human leukocyte antigen (HLA) but in this fast-moving field it is now apparent that genes outside the HLA also contribute to susceptibility. Current hypotheses concerning the pathogenesis of autoimmunity have led to the inclusion of hundreds of genes as potential candidates. Almost any molecule involved in immune recognition, cell interaction, intracellular signalling, cytokine pathways or programmed cell death can be reasonably proposed. The identification of the genes involved in complex diseases will contribute to an understanding of disease mechanisms and disease biology. The disease pathways by which the genes exert their effects or functions could lead to the discovery of new therapeutic targets that may be modulated. An increased understanding of the interactions between genes and environment might also be attained.