| Title: | Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis |
| Journal: | Current Research in Translational Medicine |
| Published: | 6 Dec 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36493747/ |
| DOI: | https://doi.org/10.1016/j.retram.2022.103374 |
Publication 10787
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: We investigated the causality of IL-8 on carotid intima-media thickness (c-IMT), a measure of sub-clinical atherosclerosis.</p>
METHODS: The IMPROVE is a multicenter European study (n = 3,711). The association of plasma IL-8 with c-IMT (mm) was estimated by quantile regression. Genotyping was performed using the Illumina CardioMetabo and Immuno chips. Replication was attempted in three independent studies and a meta-analysis was performed using a random model.</p>
RESULTS: In IMPROVE, each unit increase in plasma IL-8 was associated with an increase in median c-IMT measures (all p<0·03) in multivariable analyses. Linear regression identified rs117518778 and rs8057084 as associated with IL-8 levels and with measures of c-IMT. The two SNPs were combined in an IL-8-increasing genetic risk that showed causality of IL-8 on c-IMT in IMPROVE and in the UK Biobank (n = 22,179). The effect of IL-8 on c-IMT measures was confirmed in PIVUS (n = 1,016) and MDCCC (n = 6,103). The association of rs8057084 with c-IMT was confirmed in PIVUS and UK Biobank with a pooled estimate effect (β) of -0·006 with 95%CI (-0·008- -0·003).</p>
CONCLUSION: Our results indicate that genetic variants associated with plasma IL-8 also associate with c-IMT. However, we cannot infer causality of this association, as these variants lie outside of the IL8 locus.</p>
21 Authors
- Ilais Moreno Velásquez
- Anders Malarstig
- Damiano Baldassarre
- Yan Borne
- Ulf de Faire
- Gunnar Engström
- Per Eriksson
- Philippe Giral
- Steve E Humphries
- Sudhir Kurl
- Karin Leander
- Lars Lind
- Anders Lindén
- Nicola Orsini
- Matteo Pirro
- Angela Silveira
- Andries J Smit
- Elena Tremoli
- Fabrizio Veglia
- Rona J Strawbridge
- Bruna Gigante
Enabling scientific discoveries that improve human health