Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 30, Issue 4, Pages 885-U640Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.109.199422
Keywords
GWA study; IL-18; IL18 gene
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Funding
- NHS [U01HG004399, U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033]
- National Institute of Dental and Craniofacial Research studies [U01DE018993, U01DE018903]
- Gene Environment-Association Studies (GENEVA) under the National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI)
- GENEVA Coordinating Center [U01HG004446]
- NIH GEI [U01HG04424, U01HG004438]
- NIH [HHSN268200782096C, R01-HL71981]
- National Cancer Institute [P01-CA087969, P01-CA055075]
- National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK058845]
- Boston Obesity Nutrition Research Center [DK46200]
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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 1X10(-5) significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31X10(-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<5X10(-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. Conclusion-This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels. (Arterioscler Thromb Vasc Biol. 2010; 30: 885-890.)
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