Viatte S et al. – In the largest sample size studied to date, the authors have shown that the strength of association, the effect size and the number of known rheumatoid arthritis (RA) susceptibility loci associated with disease is different in the two disease serotypes, confirming the hypothesis that they might be two genetically different subsets.Methods
- RA patients and controls, with serological and genetic data, were available from UK Caucasian patients (n=4068 anti–CCP positive, 2040 anti–CCP negative RA) and 13,009 healthy controls.
- HLA–DRB1 genotypes and 36 single nucleotide polymorphisms were tested for association between controls and anti–CCP positive or negative RA.
- The shared epitope (SE) showed a strong association with anti–CCP positive and negative RA, although the effect size was significantly lower in the latter (effect size ratio=3.18, p<1.0E–96).
- A non–intronic marker at TNFAIP3, GIN1/C5orf30, STAT4, ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility, irrespective of the serological status, the latter three markers remaining significantly associated with anti–CCP negative RA, after correction for multiple testing.
- No significant association with anti–CCP negative RA was detected for other markers (eg, AFF3, CD28, intronic marker at TNFAIP3), though the study power for those markers was over 80%.