Dutch researchers have identified two polymorphisms on chromosome 6q23 that are associated with an increased rate of joint destruction in some patients with rheumatoid arthritis (RA).
“This is the first study demonstrating such an effect for genetic polymorphisms located outside the human leukocyte antigen (HLA)-region in anti-citrullinated peptide antibodies (ACPA)-positive RA patients,” write René Toes (Leiden University Medical Center) and co-authors.
Previously, a genetic polymorphism in the 6q23 region has been detected in patients with long-standing disease but not those with early arthritis, the team explains.
To investigate further, the researchers examined 324 Dutch patients with early RA who were followed-up for radiographic joint damage over 5 years. ACPA were present in 181 patients and absent in 143.
The patients were genotyped at five single nucleotide polymorphisms in the 6q23 region - rs1878658, rs675520, rs9376293, rs10499194, and rs6920220.
As reported in the Annals of Rheumatic Disease, there was no overall association between any of the genotypes and radiographic joint damage. However, analysis showed that two of the genotypes were associated with joint damage among ACPA-positive patients.
Carriers ofthe G allele of rs675520 had higher Sharp van der Heijdge radiograph scores over time compared with homozygotes for the A allele.
A similar relationship was also detected between carriage of the C allele of rs9376293 and greater radiographic joint damage compared with homozygotes for the T allele.
Toes et al say that further research is required into the relationship between the 6q23 region and joint destruction.
Nevertheless, they note that the closest functional known genes to the 6q23 region are tumor necrosis factor-induced protein 3 (TNFAIP3), which encodes a protein called A20 that suppresses NF-kappaB activity.
“This observation makes TNFAIP3/A20 and the 6q23 region interesting candidates that could modulate inflammation also in RA,” the researchers conclude.