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The severity of joint damage progression in rheumatoid arthritis (RA) is heritable. Several genetic variants have been identified, but together explain only part of the total genetic effect. Variants in  Interleukin-6 (IL-6), Interleukin-10 (IL-10), C5-TRAF1,  and  Fc-receptor-like-3 (FCRL3)  have been described to associate with radiographic progression, but results of different studies were incongruent. We aimed to clarify associations of these variants with radiographic progression by evaluating six independent cohorts.    Methods  In total 5,895 sets of radiographs of 2,493 RA-patients included in six different independent datasets from the Netherlands, Sweden, Spain and North-America were studied in relation to rs1800795  (IL-6) , rs1800896  (IL-10),  rs2900180 ( C5-TRAF1)  and rs7528684  (FCRL3) . Associations were tested in the total RA-populations and in anti-citrullinated peptide antibodies (ACPA)-positive and ACPA-negative subgroups per cohort, followed by meta-analyses. Furthermore, the associated region  C5-TRAF1  was fine-mapped in the ACPA-negative Dutch RA-patients.    Results  No associations were found for rs1800795  (IL-6) , rs1800896  (IL-10)  and rs7528684  (FCRL3)  in the total RA-population and after stratification for ACPA. Rs2900180 in  C5-TRAF1  was associated with radiographic progression in the ACPA-negative population ( P -value meta-analysis = 5.85 × 10 −7 ); the minor allele was associated with more radiographic progression. Fine-mapping revealed a region of 66Kb that was associated; the lowest  P -value was for rs7021880 in  TRAF1 . The  P -value for rs7021880 in meta-analysis was 6.35 × 10 −8 . Previous studies indicate that the region of rs7021880 was associated with RNA expression of  TRAF1  and  C5 .    Conclusion  Variants in  IL-6, IL-10  and  FCRL3  were not associated with radiographic progression. Rs2900180 in  C5-TRAF1  and linked variants in a 66Kb region were associated with radiographic progression in ACPA-negative RA.    Electronic supplementary material  The online version of this article (doi:10.1186/s13075-014-0514-0) contains supplementary material, which is available to authorized users.

A genetic study on C5-TRAF1 and progression of joint damage in rheumatoid arthritis