Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis

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. StrawbridgeBruna Gigante*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Abstract

Background: We investigated the causality of IL-8 on carotid intima-media thickness (c-IMT), a measure of sub-clinical atherosclerosis. 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. 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 MDC–CC (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). 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.

Original languageEnglish
Article number103374
Number of pages9
JournalCurrent Research in Translational Medicine
Volume71
Issue number1
DOIs
Publication statusPublished - 1-Jan-2023

Keywords

  • Carotid intima media thickness
  • Chemokines
  • Cohort studies
  • Genetic association studies
  • Subclinical atherosclerosis

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