Background Family history of rheumatoid arthritis (RA) is a surrogate for an individual's genetic and partly environmental risk of developing RA. It is assessed daily in clinical practice and its magnitude and pattern of distribution may provide information on the RA etiology.
Objectives We investigated the association between family history of RA and the risk of anti-citrullinated peptide antibody (ACPA)-positive and ACPA-negative RA in the Malaysian population.
Methods Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study involving 1,055 early RA cases and 1,055 age, sex and residential area-matched controls were analyzed. Information from interview-reported family history of RA or rheumatic stiff back among first degree relatives was used to estimate the risk of developing ACPA-positive and ACPA negative RA. The odds ratio (OR) with 95% confidence interval (CI) was calculated.
Results In this study, 64% of the RA patients were ACPA-positive and 40% of the overall RA carried HLA-DRB1 shared epitope (SE) alleles. Family history of RA was significantly associated with an increased risk of developing RA in the Malaysian population (RA versus controls, 17.0% vs. 7.7%, OR 2.4, 95% CI 1.8–3.2, p<0.0001). The association between positive family history and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.8–3.3, p<0.0001) and ACPA-negative RA (OR 2.3, 95% CI 1.6–3.2, p<0.0001) subsets, respectively. A dramatically increased risk for ACPA-positive RA was seen in individuals who both were having positive family history of RA and carried HLA-DRB1 SE alleles (OR 14.7, 95% CI 7.7–27.8). We also observed a lesser risk magnitude in the ACPA-negative RA patients (OR 5.7, 95% CI 2.7–11.9).
Conclusions Our data demonstrate that family history of RA remains an important clinical risk factor for RA. In addition, positive family history of RA was associated with an increased risk of developing both the ACPA-positive and ACPA-negative RA in the Malaysian population, suggesting that the two RA subsets are similar in genetic risk factors that overlap with these diseases.
Frisell T, Saevarsdottir S, Askling J. Family history of rheumatoid arthritis: an old concept with new developments. Nat Rev Rheumatol. 2016 Jun;12(6):335–43.
Frisell T, Hellgren K, Alfredsson L, Raychaudhuri S, Klareskog L, Askling J. Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden. Ann Rheum Dis. 2016 Jan;75(1):183–9.
Disclosure of Interest None declared