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 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.
Gracie
J A
JA
Centre for Rheumatic Diseases, University of Glasgow, Glasgow, Scotland, UK.
Koyama
N
N
Murdoch
J
J
Field
M
M
McGarry
F
F
Crilly
A
A
Schobel
A
A
Madhok
R
R
Pons-Kühnemann
J
J
McInnes
I B
IB
Möller
B
B
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
D020382:Interleukin-18