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.

Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis / I.M. Velásquez, A. Malarstig, D. Baldassarre, Y. Borne, U. de Faire, G. Engström, P. Eriksson, P. Giral, S.E. Humphries, S. Kurl, K. Leander, L. Lind, A. Lindén, N. Orsini, M. Pirro, A. Silveira, A.J. Smit, E. Tremoli, F. Veglia, R.J. Strawbridge, B. Gigante. - In: CURRENT RESEARCH IN TRANSLATIONAL MEDICINE. - ISSN 2452-3186. - 71:1(2023 Mar), pp. 103374.1-103374.9. [10.1016/j.retram.2022.103374]

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

D. Baldassarre
Membro del Collaboration Group
;
E. Tremoli
Membro del Collaboration Group
;
F. Veglia
Membro del Collaboration Group
;
2023

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 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.
Carotid intima media thickness; Chemokines; Cohort studies; Genetic association studies; Subclinical atherosclerosis
Settore BIO/14 - Farmacologia
6-dic-2022
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/948129
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