title: 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=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 chi(2) tests suggested that -607CC was overrepresented in German, and -137CC in Scottish RA patients, but conservative chi(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.
authors.affiliation: Centre for Rheumatic Diseases, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Gracie
authors.forename: N
authors.initials: N
authors.lastname: Koyama
authors.forename: J
authors.initials: J
authors.lastname: Murdoch
authors.forename: M
authors.initials: M
authors.lastname: Field
authors.forename: F
authors.initials: F
authors.lastname: McGarry
authors.forename: A
authors.initials: A
authors.lastname: Crilly
authors.forename: A
authors.initials: A
authors.lastname: Schobel
authors.forename: R
authors.initials: R
authors.lastname: Madhok
authors.forename: J
authors.initials: J
authors.lastname: Pons-Kühnemann
authors.forename: I B
authors.initials: IB
authors.lastname: McInnes
authors.forename: B
authors.initials: B
authors.lastname: Möller
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D005858:Germany; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012606:Scotland; D044465:White People
chemical_list: D020382:Interleukin-18