• Alexander P Reiner, Mark M Wurfel, Leslie A Lange, Christopher S Carlson, Alex S Nord, Cara L Carty, Mark J Rieder, Cindy Desmarais, Nancy S Jenny, Carlos Iribarren, Jeremy D Walston, O Dale Williams, Deborah A Nickerson, and Gail P Jarvik.
• Department of Epidemiology, Box 357236, University of Washington, Seattle, Washington 98195, USA. apreiner@u.washington.edu
• Arterioscler. Thromb. Vasc. Biol. 2008 Jul 1;28(7):1407-12.

BackgroundCirculating 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 ResultsWe 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.ConclusionsCommon functional polymorphisms of the IL1RN gene are associated with several markers of systemic inflammation.

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