The heritability of RA is estimated to be 53-65% in the Finnish and UK data.
Factors known to increase risk of RA.
Genetic risk factors
The main genetic factor is HLA-DRB1*04 and *01 clusters which encode the "shared-epitope" sequences in MHC region.
Polymorphisms of PTPN22, TRAF1-C5 and TNFAIP3 have also been described in RA.
However more than half of the genetic risk factors remain to be identified.
Environmental risk factors
Smoking is the main environmental risk factor associated with RA.
Several microorganisms have been implicated in the development of RA.
Pollutants may affect the risk of developing RA.
Women living within 50m of a road had an increased risk of RA (hazard ratio,1.31) compared to 200m.
High birth weight was positively associated with RA(OR, 3.3).
Other risk factors
RA is far more common in women then in men (3:1).
Gene-environment interactions may have a synergistic
effect on RA. In a population-based case-control study, the risk was
higher in smokers carrying two copies of shared-epitope genes (RR, 15.7)
than in smokers with no copies (RR, 2.4).
The peak age at RA onset is the fifth decade. However, recent studies suggest a shift toward an older age at onset.
North America and Northern Europe populations are at higher risk for RA than others.
Protective factors
Hormone replacement therapy (HRT) may decrease the RA risk in women who carry the HLA-DRB1 alleles.
Breast feeding was protective to RA (OR, 0.3).
A diet rich in fish, olive oil, and cooked vegetables has been shown to protect against RA.
Tobón GJ, et al. Autoimmun. Rev. 2010 Mar;9(5).
