Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

Interleukin (IL)-18 is an important mediator of innate and adaptive immunity. We searched for an association of IL-18 promoter single-nucleotide polymorphisms (SNP) with rheumatoid arthritis (RA) in Caucasians. The entire study population was composed of two independent cohorts from Germany ( n =200) and Scotland ( n =410). Presence of IL-18 SNP at positions −607 and −137 was determined by allele-specific PCR in 327 RA patients and 283 healthy donors (HD). Diplotype distributions of both loci were in Hardy–Weinberg equilibrium (HWE) in the German and Scottish HD cohorts. In contrast, locus −607 was in HW disequilibrium in German, and locus −137 in Scottish RA patients. Diplotypic exact χ 2 tests suggested that −607CC was overrepresented in German, and −137CC in Scottish RA patients, but conservative χ 2 trend analyses could not prove any significant disease association of these single loci. SNP −607 and −137 were in strong linkage disequilibrium. The −607C * −137C haplotype was more prevalent in German RA (3.2 vs 1.2%) and in Scottish RA patients (4.1 vs 0.9%) than in the respective HD cohorts. These observations suggest that SNP of both positions contribute to the genetic background of RA pathogenesis.