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Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1407-12. doi: 10.1161/ATVBAHA.108.167437. Epub 2008 May 1.

Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation.

Author information

1
Department of Epidemiology, Box 357236, University of Washington, Seattle, Washington 98195, USA. apreiner@u.washington.edu

Abstract

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.

METHODS AND 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.

PMID:
18451331
PMCID:
PMC2748384
DOI:
10.1161/ATVBAHA.108.167437
[Indexed for MEDLINE]
Free PMC Article

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