Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation.
BACKGROUND
Circulating levels of acute phase reactant proteins such as plasma C-reactive protein (CRP) are likely influenced by multiple genes regulating the innate immune response.


RESULTS
We screened a set of 16 inflammation-related genes for association with CRP in a large population-based study of healthy young adults (n=1627). Results were validated in 2 independent studies (n=1208 and n=4310), including a pooled analysis of all 3 studies. In the pooled analysis, the minor allele of IL1RN 1018 (rs4251961) within the gene encoding interleukin (IL)-1 receptor antagonist (IL-1RA) was significantly associated with higher mean plasma log(CRP) level (P<1 x 10(-4)). The same IL1RN 1018 allele was associated with higher mean plasma log(IL-6) levels (P=0.004). In the pooled analysis, the minor allele of IL1RN 13888 (rs2232354) was associated with higher fibrinogen, (P=0.001). The IL1RN 1018 and 13888 variant alleles tag a clade of IL1RN haplotypes linked to allele 1 of an 86-bp VNTR polymorphism. We confirmed that the IL1RN 1018 variant (rs4251961) was associated with decreased cellular IL-1RA production ex vivo.


CONCLUSIONS
Common functional polymorphisms of the IL1RN gene are associated with several markers of systemic inflammation.
Reiner
Alexander P
AP
Department of Epidemiology, Box 357236, University of Washington, Seattle, Washington 98195, USA. apreiner@u.washington.edu
Wurfel
Mark M
MM
Lange
Leslie A
LA
Carlson
Christopher S
CS
Nord
Alex S
AS
Carty
Cara L
CL
Rieder
Mark J
MJ
Desmarais
Cindy
C
Jenny
Nancy S
NS
Iribarren
Carlos
C
Walston
Jeremy D
JD
Williams
O Dale
OD
Nickerson
Deborah A
DA
Jarvik
Gail P
GP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D018836:Inflammation Mediators / Q000097:blood*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors; D014481:United States
D015415:Biomarkers; C507763:IL1RN protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D002097:C-Reactive Protein