Velásquez, Ilais Moreno;
Malarstig, Anders;
Baldassarre, Damiano;
Borne, Yan;
de Faire, Ulf;
Engström, Gunnar;
Eriksson, Per;
... Gigante, Bruna; + view all
(2022)
Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis.
Current Research in Translational Medicine
, 71
(1)
, Article 103374. 10.1016/j.retram.2022.103374.
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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 MDCCC (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.
| Type: | Article |
|---|---|
| Title: | Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis |
| Location: | France |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.retram.2022.103374 |
| Publisher version: | https://doi.org/10.1016/j.retram.2022.103374 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Carotid intima media thickness, Chemokines, Cohort studies, Genetic association studies, Subclinical atherosclerosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10161989 |
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