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

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.; Gigante, B.

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:	Moreno Velásquez, I. ORCID: https://orcid.org/0000-0001-6058-8983, 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.
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
ISSN:	2452-3186
Publisher:	Elsevier
Volume:	71
Number:	1
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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