Genetic studies in the rheumatic diseases: present status and implications for the future.
Recent breakthroughs in genetic methodology have greatly augmented our understanding of the contribution of genetics to susceptibility to the rheumatic diseases. Disorders in which familial aggregation has been best documented include rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). Much of the genetic contribution to these diseases lies in the MHC, including HLA-DR4 (RA), HLA-B27 (AS), HLA-DRB1*0301, DRB1*1501/*1503, DRB1*08, and C4 null alleles (SLE), and HLA-DRB1*11 and DRB1*1502 (SSc). Genome-wide scans have provided inconsistent data in RA, although consistent regions have been observed in scans from different groups in AS and SLE. No consistent non-MHC candidate gene has been identified in RA. There is active investigation in AS in this area. In SLE the Fc gamma RIIa and Fc gamma IIIa genes have been most thoroughly described, and in SSc fibrillin and SPARC. Newer techniques being developed presently, such as high density single nucleotide polymorphism genome-wide scanning, show promise to bring these analyses to the next level, which will hopefully result not only in better screening of individuals at highest risk, but also in novel treatments.
Reveille
John D
JD
Division of Rheumatology and Clinical Immunogenetics, University of Texas-Houston Health Science Ctr., Houston, Texas 77030, USA. john.reveille@uth.tmc.edu
D005192:Family Health; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007391:International Cooperation; D008285:Major Histocompatibility Complex / Q000235:genetics; D012216:Rheumatic Diseases / Q000235:genetics*; D012219:Rheumatology / Q000639:trends*