Alleles and rheumatoid arthritis

Abstract:

Rheumatoid Arthritis (RA) is a polygenic, complex, and disabling disease that affects joints in a symmetric and progressive manner. This disorder has a genetic component, thus pbkp_redisposing genes influence both occurrence and symptom severity. Beyond pbkp_redispositional genes influencing susceptibility, there also exist genes that are unrelated to etiology and still others that may have protective attributes. Contemporary research has, however, been unable to elucidate the exact mechanism by which these genes act as causatives or protective. HLA-DRβ1 represent the group of genes that have demonstrated clearly to have a significant role in the development of RA; an association that was found primarily with Stastny (1976) and established in numerous confirmatory investigations worldwide. The Major Histocompatibility Complex (MHC) is a region located in chromosome 6 (6p21.3) that encompasses three sub-regions: HLA class I, class II, and class III. The genes HLA-DRβ1 are highly polymorphic and belong to class II, and a number appear to be key to the development and progress of RA. HLA-DR4, for example, has been the most reported gene for RA susceptibility around the world. High resolution HLA typing, has allowed researchers to find several subtypes of DR4, leading to the conclusion that not all the DR4 alleles have the same role in RA onset and progression. The shared epitope (SE) is a sequence commonly found in some HLA-DRβ1 alleles, between the amino acid residues 70 to 74, forming a part of the antigen binding site. Interestingly these alleles have been found to be RA risk factors. DRβ1*0401, *0404, *0405, and *0101, for example, have been reported in several case-control and familiar studies. Other genes like TNFα, PTPN22, and those comprised in the MHC region have also been associated with RA. The mechanism by which the alleles from this region participate as immunoregulatory factors would be clarified when robust and replicable evidence at levels of cell signalling, T cells function, and serological and clinical factors are confirmed. HLA typing studies can be performed to partially achieve these objectives, usually within the context of case-control or familiar surveys. Researchers and pharmaceutical companies currently face the to elucidate the role of the molecules, receptors, and genes involved in RA, in order to produce more effective medicines and treatments to relieve the symptoms, or even to prevent the manifestation of this distressing pathology.

Año de publicación:

2012

Keywords:

Fuente:

scopus