Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels.
Interleukin-1-receptor antagonist (IL-1RA) modulates the biological activity of the proinflammatory cytokine interleukin-1 (IL-1) and could play an important role in the pathophysiology of inflammatory and metabolic traits. We genotyped seven single nucleotide polymorphisms (SNPs) that capture a large proportion of common genetic variation in the IL-1RN gene in 1256 participants from the Invecchiare in Chianti study. We identified five SNPs associated with circulating IL-1RA levels with varying degrees of significance (P-value range=0.016-4.9 x 10(-5)). We showed that this association is likely to be driven by one haplotype, most strongly tagged by rs4251961. This variant is only in weak linkage disequilibrium (r(2)=0.25) with a previously reported variable number of tandem repeats polymorphism (VNTR) in intron-2 although a second variant, rs579543, that tags the VNTR (r(2)=0.91), may also be independently associated with IL-1RA levels (P=0.03). We found suggestive evidence that the C allele at rs4251961 that lowers IL-1RA levels is associated with an increased IL-1beta (P=0.03) level and may also be associated with interferon -gamma (P=0.03), alpha-2 macroglobulin (P=0.008) and adiponectin (P=0.007) serum levels. In conclusion, common variation across the IL-1RN gene is strongly associated with IL-1RA levels.
Rafiq
S
S
Peninsula College of Medicine and Dentistry, University of Exeter, Magdalen Road, Exeter, UK.
Stevens
K
K
Hurst
A J
AJ
Murray
A
A
Henley
W
W
Weedon
M N
MN
Bandinelli
S
S
Corsi
A M
AM
Guralnik
J M
JM
Ferruci
L
L
Melzer
D
D
Frayling
T M
TM
D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D014644:Genetic Variation; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D007558:Italy; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
D053590:Interleukin 1 Receptor Antagonist Protein