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

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Item Type:Article
Title:Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis
Creators Name:Velásquez, I.M. and Malarstig, A. and Baldassarre, D. and Borne, Y. and de Faire, U. and Engström, G. and Eriksson, P. and Giral, P. and Humphries, S.E. and Kurl, S. and Leander, K. and Lind, L. and Lindén, A. and Orsini, N. and Pirro, M. and Silveira, A. and Smit, A.J. and Tremoli, E. and Veglia, F. and Strawbridge, R.J. and Gigante, B.
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 MDCCC (n = 6,103). The association of rs8057084 with c-IMT was confirmed in PIVUS and UK Biobank with a pooled estimate effect (ß) 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.
Keywords:Chemokines, Genetic Association Studies, Subclinical Atherosclerosis, Carotid Intima Media Thickness, Cohort Studies
Source:Current Research in Translational Medicine
Page Range:103374
Date:January 2023
Official Publication:https://doi.org/10.1016/j.retram.2022.103374
PubMed:View item in PubMed

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