Quantitative heritability of anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis, van der Woude et al, 2009
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What did they study?
Rheumatoid arthritis patients tend to be positive for anti-citrullinated protein antibody (ACPA), with 67% of patients testing positive. Patients who are ACPA positive tend to have a higher rate of joint destruction than seronegative patients, and a positive result is also more predictive of patient outcomes (i.e., how sick they will become) than RF.
Although several genes have been linked to ACPA-positive RA, the gene HLA-DRB1 is the most associated with ACPA-positive RA. In this study, the researchers examined pairs of identical and fraternal twins in which at least one of the twins had RA to examine the heritability of RA overall as well as ACPA seropositivity or negativity.
A total of 64 identical twins (of which 74 had RA) and 84 fraternal twins (of which 87 had RA) were studied. Concordance, which is a measure of the likelihood both twins in a pair will both have RA, and heritability, which is a measure of the amount that genetic differences affect the likelihood of developing RA, were measured.
What were the results?
In identical twin pairs, if one twin had RA the other was much more likely to have RA (15.6% concordance compared to 3.6% in fraternal twins). The heritability was 66%, meaning that genetic factors have a significant effect on the likelihood an individual will develop RA. ACPA-positive and negative RA were similarly heritable.
ACPA-positive people tended to have the HLA-DRB1 gene (89%), while many fewer (47%) ACPA-negative people did.
What does this mean?
This study demonstrated again that RA is clearly impacted by an individual's genetic makeup. However, while there is clearly a link between this particular gene and seropositive RA, the results are clearly impacted by the overall low number of people who were ACPA-negative (with RA) on the study. Further study on the genome of positive and especially negative patients is needed to determine a clear pattern of genes that could indicate a patient is very likely to develop RA.
As discussed in the previous post, early diagnosis and treatment is vital to reducing disability and increasing remission rates. If people can understand their risk, they are more likely to be able to realize the significance of early RA symptoms and seek treatment early.
