Recent studies have identified 6q23 as an important susceptibility locus for rheumatoid arthritis (RA), with risk alleles at 3 single-nucleotide polymorphisms combining to give an effect size greater than that of these markers individually. We investigated whether these polymorphisms are also associated with disease severity measured by radiological damage.
We studied 927 patients from a cross-sectional RA cohort. Median Larsen scores (LS) read from radiographs taken at study entry were compared by genotype at rs6920220, rs13207033, and rs5029937 according to a dominant model using negative binomial regression with stratification for autoantibody status.
Median LS was associated with genotype at rs6920220 [LS 31 GG vs 36 GA/AA (p=0.02) in cyclic citrullinated peptide+ (CCP) RA] and rs13020220 [LS 37 GG vs 29 GA/AA (p=0.02) in CCP+ RA] only in autoantibody-positive RA, with no association at rs5029937. Association was stronger for these markers in combination [LS 28 vs 42 for lowest vs highest risk genotype combination in rheumatoid factor positivity (p=0.007), LS 28 vs 37 for anti-CCP+ (p=0.01)].
Established RA risk markers at 6q23 are associated also with radiographic severity in autoantibody-positive RA; as for susceptibility, the association for these markers in combination is stronger than that for markers alone.