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

Alexander P. Reiner, Mark M. Wurfel, Leslie A. Lange, Christopher S. Carlson, Alexander Nord, Cara L. Carty, Mark J. Rieder, Cindy Desmarais, Nancy S. Jenny, Carlos Iribarren, Jeremy D. Walston, O. Dale Williams, Deborah A. Nickerson, Gail P. Jarvik

Research output: Contribution to journalArticle

65 Citations (Scopus)

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<1×10). 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.

Original languageEnglish (US)
Pages (from-to)1407-1412
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume28
Issue number7
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

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Interleukin-1 Receptors
Alleles
Inflammation
C-Reactive Protein
Acute-Phase Proteins
Genes
Interleukins
Innate Immunity
Fibrinogen
Haplotypes
Blood Proteins
Young Adult
Interleukin-6
Population

Keywords

  • C-reactive protein
  • Fibrinogen
  • IL-1 receptor antagonist
  • Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation. / Reiner, Alexander P.; Wurfel, Mark M.; Lange, Leslie A.; Carlson, Christopher S.; Nord, Alexander; Carty, Cara L.; Rieder, Mark J.; Desmarais, Cindy; Jenny, Nancy S.; Iribarren, Carlos; Walston, Jeremy D.; Williams, O. Dale; Nickerson, Deborah A.; Jarvik, Gail P.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 28, No. 7, 01.07.2008, p. 1407-1412.

Research output: Contribution to journalArticle

Reiner, AP, Wurfel, MM, Lange, LA, Carlson, CS, Nord, A, Carty, CL, Rieder, MJ, Desmarais, C, Jenny, NS, Iribarren, C, Walston, JD, Williams, OD, Nickerson, DA & Jarvik, GP 2008, 'Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 7, pp. 1407-1412. https://doi.org/10.1161/ATVBAHA.108.167437
Reiner, Alexander P. ; Wurfel, Mark M. ; Lange, Leslie A. ; Carlson, Christopher S. ; Nord, Alexander ; Carty, Cara L. ; Rieder, Mark J. ; Desmarais, Cindy ; Jenny, Nancy S. ; Iribarren, Carlos ; Walston, Jeremy D. ; Williams, O. Dale ; Nickerson, Deborah A. ; Jarvik, Gail P. / Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2008 ; Vol. 28, No. 7. pp. 1407-1412.
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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<1×10). 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.",
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AU - Reiner, Alexander P.

AU - Wurfel, Mark M.

AU - Lange, Leslie A.

AU - Carlson, Christopher S.

AU - Nord, Alexander

AU - Carty, Cara L.

AU - Rieder, Mark J.

AU - Desmarais, Cindy

AU - Jenny, Nancy S.

AU - Iribarren, Carlos

AU - Walston, Jeremy D.

AU - Williams, O. Dale

AU - Nickerson, Deborah A.

AU - Jarvik, Gail P.

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N2 - 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<1×10). 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.

AB - 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<1×10). 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.

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