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

Moreno Velásquez, I. et al. (2023) Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis. Current Research in Translational Medicine, 71(1), 103374. (doi: 10.1016/j.retram.2022.103374) (PMID:36493747)

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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 MDCsingle bondCC (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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Strawbridge, Dr Rona
Authors: Moreno Velásquez, I., Malarstig, A., Baldassarre, D., Borne, Y., de Faire, U., Engström, G., Eriksson, P., Giral, P., Humphries, S. E., Kurl, S., Leander, K., Lind, L., Lindén, A., Orsini, N., Pirro, M., Silveira, A., Smit, A. J., Tremoli, E., Veglia, F., Strawbridge, R. J., and Gigante, B.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Current Research in Translational Medicine
ISSN (Online):2452-3186
Published Online:06 December 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Current Research in Translational Medicine 71(1): 103374
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302131Understanding the excess risk of cardiometabolic disease in individuals with serious mental illnessJill PellMedical Research Council (MRC)MR/S003061/1HW - Public Health