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

Velásquez, Ilais Moreno ; Malarstig, Anders ; Baldassarre, Damiano ; Borne, Yan LU ; de Faire, Ulf ; Engström, Gunnar LU ; Eriksson, Per ; Giral, Philippe ; Humphries, Steve E and Kurl, Sudhir , et al. (2023) In Current Research in Translational Medicine 71(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Current Research in Translational Medicine
volume
71
issue
1
article number
103374
publisher
Elsevier
external identifiers
  • pmid:36493747
  • scopus:85143883824
ISSN
2452-3186
DOI
10.1016/j.retram.2022.103374
language
English
LU publication?
yes
additional info
Copyright © 2022 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.
id
aa96e9d7-dfc6-4e19-acc3-d423fa36fafc
date added to LUP
2022-12-16 14:00:00
date last changed
2024-05-17 23:35:30
@article{aa96e9d7-dfc6-4e19-acc3-d423fa36fafc,
  abstract     = {{<p>BACKGROUND: We investigated the causality of IL-8 on carotid intima-media thickness (c-IMT), a measure of sub-clinical atherosclerosis.</p><p>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.</p><p>RESULTS: In IMPROVE, each unit increase in plasma IL-8 was associated with an increase in median c-IMT measures (all p&lt;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).</p><p>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.</p>}},
  author       = {{Velásquez, Ilais Moreno and Malarstig, Anders and Baldassarre, Damiano and Borne, Yan and de Faire, Ulf and Engström, Gunnar and Eriksson, Per and Giral, Philippe and Humphries, Steve E and Kurl, Sudhir and Leander, Karin and Lind, Lars and Lindén, Anders and Orsini, Nicola and Pirro, Matteo and Silveira, Angela and Smit, Andries J and Tremoli, Elena and Veglia, Fabrizio and Strawbridge, Rona J and Gigante, Bruna}},
  issn         = {{2452-3186}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Elsevier}},
  series       = {{Current Research in Translational Medicine}},
  title        = {{Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis}},
  url          = {{http://dx.doi.org/10.1016/j.retram.2022.103374}},
  doi          = {{10.1016/j.retram.2022.103374}},
  volume       = {{71}},
  year         = {{2023}},
}