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 1×10-5 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31×10-8). 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<5×10-8). 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. Conclusion: This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.
Original language | English (US) |
---|---|
Pages (from-to) | 885-890 |
Number of pages | 6 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 30 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2010 |
Keywords
- GWA study
- IL-18
- IL18 gene
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine