REVIEW - Recent progress in RA genetics: one step towards improved patient care

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Curr Opin Rheumatol. 2009 Apr 13.

Recent progress in rheumatoid arthritis genetics: one step towards

improved patient care.

Plenge RM.

aDivision of Rheumatology, Immunology and Allergy, Brigham and

Women's, Hospital, Harvard Medical School, Boston, USA bBroad

Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

PURPOSE OF REVIEW: Recent human genetic discoveries have increased our

understanding of rheumatoid arthritis (RA) susceptibility. These

discoveries are reviewed and placed in the context of potential

important clinical applications.

RECENT FINDINGS: Genome-wide association studies and related

methodologies have expanded the number of validated RA risk loci

beyond HLA-DRB1 'shared epitope' alleles to include additional major

histocompatibility complex risk alleles and more than 10 regions

outside the major histocompatibility complex locus. The newly

discovered risk alleles are common in the general population, and most

have a modest effect on risk of RA (odds ratio approximately 1.15 per

copy of each risk allele). Although the actual causal mutation and

causal gene for most loci remain to be determined, these studies are

beginning to reveal general themes: many risk loci are associated with

other autoimmune diseases, many genes fall within discrete biological

pathways (e.g., the NF-kappaB signaling pathway), and human genetics

can subset disease into clinically meaningful categories (e.g.,

presence or absence of autoantibodies).

SUMMARY: Approximately one-third of the genetic basis of RA can be

explained by known risk loci. Future studies need to pinpoint the

actual causal mutations, expand the number of risk loci, and translate

these discoveries to improve care of patients with RA.

PMID: 19365266

http://www.ncbi.nlm.nih.gov/pubmed/19365266

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