IL10.G microsatellites mark promoter haplotypes associated with protectionagainst the development of reactive arthritis in Finnish patients

Objective. To investigate the association of microsatellites and single-nuc leotide promoter polymorphisms (SNPs) in the gene for the cytokine interleu kin-10 (IL-10) with susceptibility to and outcome of reactive arthritis (Re A). Methods. From genomic DNA, IL-10 microsatellites G and R and IL-10 promoter polymorphisms at positions -1087 and -524 were typed by polymerase chain r eaction, automated fragment length analysis, and restriction fragment diges tion in 85 Finnish patients with ReA and 62 HLA-B27-positive Finnish contro ls. ReA patients had been followed up for 20 years. Genotypes and haplotype s of IL-10 were correlated with distinct features of the disease course, su ch as triggering agent, chronic arthritis, development of ankylosing spondy litis, and other chronic features. Results. There was a significant decrease in the promoter alleles G12 (alle le frequency 0.206 versus 0.033; corrected P < 0.001, odds ratio 0.14) and G10 (0.183 versus 0.092; P < 0.05, odds ratio 0.44) in the ReA group compar ed with the HLA-B27-positive controls. Chronic arthritis developed signific antly more frequently in the B27-positive subjects than in the B27-negative subjects (P < 0.05) as well as in patients without the IL10.G8 allele. No associations were observed for either SNP or for the IL10.R microsatellite polymorphism. Conclusion. IL10.G12 and G10 microsatellite alleles show a strong protectiv e effect against the development of ReA in Finnish subjects. Since these po lymorphic markers themselves do not have direct functional implications, th ey most likely mark promoter haplotypes with distinct functional properties , suggesting that differential production of IL-10 is an important suscepti bility factor for the development of ReA.