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Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):885-90. doi: 10.1161/ATVBAHA.109.199422. Epub 2010 Feb 11.

Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels.

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  • 1Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.

Abstract

OBJECTIVE:

Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes. We sought to identify the common genetic variants associated with IL-18 levels.

METHODS AND RESULTS:

We performed a 2-stage genome-wide association study among women of European ancestry from the Nurses' Health Study (NHS) and Women's Genome Health Study (WGHS). IL-18 levels were measured by ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1 x 10(-5) significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31 x 10(-8)). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance level (P<5 x 10(-8)). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P=0.0002 and 0.0006, respectively). The 2 SNPs together explained 2.9% of variation of plasma IL-18 levels.

CONCLUSIONS:

This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.

PMID:
20150558
[PubMed - indexed for MEDLINE]
PMCID:
PMC2841960
Free PMC Article
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