Identifying Genetic Risk Factors for Rheumatoid Arthritis

New research from the Netherlands, and published in the journal Arthritis & Rheumatism has shown that genetic factors for rheumatoid arthritis (RA) may be a useful tool for determining patients at risk for the disease.

The study included 148 sets of twins, of whom at least one of the twins had RA. Factors they were studied for included ACPAs, HLA-DRB1 genotypes, and HLA SE alleles.

Patients were tested for anti-citrullinated protein antibodies (ACPAs), which are known for their predictive value, and HLA SE (human leukocyte antigen shared epitope) alleles, the most significant genetic risk factor for RA. Patients with both ACPA-positive and ACPA-negative RA were found to have different genetic and environmental risk factors for the disease and “may constitute distinct entities with different disease mechanisms,” according to the results. In addition, 66 percent of both ACPA-positive and ACPA-negative RA were heritable.

In a second finding, the HLA SE alleles accounted for 11 percent of the total genetic variance for RA and eight percent to the genetic variance of ACPA-positive RA, but only about two percent to the genetic variance of ACPA-negative RA.

The researchers commented that the study was conducted to “quantify the contribution of genetic risk factors in general, and of the predisposing HLA-DRB1 shared epitope (SE) alleles in particular, to the ACPA-positive and ACPA-negative subsets of RA.”

Although genetic risk factors for RA have been identified, the researchers suggested that because many of them have focused on ACPA-positive RA, the results of this new study may provide more information on the genetic risk factors for ACPA-negative RA.

The heritability of ACPA-positive RA is comparable with that of ACPA-negative RA,” the conclusion section of the journal abstract reads. “These data indicate that genetic predisposition plays an important role in the pathogenesis of ACPA-negative RA, for which most individual genetic risk factors remain to be identified.”