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

Abstract

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 ¼ 200) and Scotland (n ¼ 410). Presence of IL-18 SNP at positions À607 and À137 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 À607 was in HW disequilibrium in German, and locus À137 in Scottish RA patients. Diplotypic exact w 2 tests suggested that À607CC was overrepresented in German, and À137CC in Scottish RA patients, but conservative w 2 trend analyses could not prove any significant disease association of these single loci. SNP À607 and À137 were in strong linkage disequilibrium. The À607C*À137C 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.

Genetic Polymorphism of Interleukin-18 Gene Promoter Region in Rheumatoid Arthritis Patients from Southern India

“…Huang et al, [27] reported that IL-18-607 polymorphism was associated with RA, but not with IL-18-137 polymorphisms. Gracie et al, [28] reported that both SNPs found at positions -137 and -607 were involved in pathogenesis of RA. When other auto immune diseases were considered, the results were found to be very conflicting.…”

Disease association of the interleukin-18 promoter polymorphisms in Taiwan Chinese systemic lupus erythematosus patients

“…43 However, in Caucasian RA patients, the conclusion is not the same in Chinese RA patients. 44 The À607C-137C haplotype was more prevalent in German RA and in Scottish RA patients than in the controls. In both German and Scottish population, both SNPs at position À607 and À137 contribute to the genetic background of RA pathogenesis.…”

Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis

“…Therefore, the conclusion is that studied polymorphisms within the IL-18 promoter region do not play a major role in RA predisposition. Gracie et al (2005) found that the -607C/-137C haplotype was more prevalent in Caucasian RA patients than in a control group and concluded that SNP of both positions contribute to the genetic background of RA pathogenesis. Lee et al (2007) reported a significantly higher frequency of the 105A allele of the IL-18-105A/C SNP in Chinese rheumatoid arthritis patients compared with controls.…”