A genetic variant in the region of MMP-9 is associated with serum levels and progression of joint damage in rheumatoid arthritis

Objectives The severity of joint destruction is highly variable between rheumatoid arthritis (RA) patients. The majority of its heritability is still unexplained. Several autoimmune diseases share genetic risk variants that may also influence disease progression. We aimed to identify genetic risk factors for the severity of joint damage in RA by studying genetic susceptibility loci of several autoimmune diseases.Methods In phase 1, 3143 sets of x-rays of 646 Dutch RA patients taken over 7 years (Sharp van der Heijde (SHS) scored) were studied. Genotyping was done by Immunochip. Associations of single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) >0.01 and joint destruction were analysed. In phase 2, 686 North American RA patients with 926 SHS-scored x-rays over 15 years of follow-up were evaluated. In both phases multiple testing corrections were done for the number of uncorrelated SNPs; the thresholds for significance were pResults In phase 1, 109 SNPs associated significantly with joint destruction (pConclusions These data indicate that two loci that confer risk to other autoimmune diseases also affect the severity of joint destruction in RA. Rs11908352 may influence joint destruction via MMP-9 production.