Rheumatoid arthritis (RA) is a multifactorial disease due to a combination of 
genetic and environmental factors. Identification of the genetic factors 
involved in the pathogenesis of RA should open up avenues for developing radical 
treatment strategies directed at the cause of the disease. The Association de 
Recherche sur la Polyarthrite (ARP) supports research in this field, in which 
our group has been involved since 1993. Thanks to this support, considerable 
progress has been made. Several combinations of susceptibility alleles of 
various genes are probably involved in the development of RA. Although HLA-DRB1 
is the main RA gene, it accounts for only part of the familial risk for RA. 
HLA-DRB1 alleles are neither necessary nor sufficient to cause the development 
of RA in a given individual. Several genome scans conducted in populations from 
France, Japan, North America and UK have confirmed the role of the HLA region 
and suggested several other susceptibility loci. Association studies support a 
role for several genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22. 
However, the imperfect matching of cases and controls requires that confirmation 
of these results be obtained. To confirm that a gene confers susceptibility to 
RA, the association must be replicated in several independent studies and, more 
importantly, evidence of genetic linkage must be obtained in family studies. The 
identification of genetic factors conferring susceptibility to RA will open up 
new avenues toward radical treatments for RA and may help to optimize the 
diagnostic, prognostic, and pharmacogenetic management of today's patients with 
RA.