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

Ilais Moreno Velásquez; Anders Malarstig; Damiano Baldassarre; Yan Borne; Ulf de Faire; Gunnar Engström; Per Eriksson; Philippe Giral; Steve E Humphries; Sudhir Kurl; Karin Leander; Lars Lind; Anders Lindén; Nicola Orsini; Matteo Pirro; Angela Silveira; Andries J Smit; Elena Tremoli; Fabrizio Veglia; Rona J Strawbridge; Bruna Gigante

doi:10.1016/j.retram.2022.103374

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

Ilais Moreno Velásquez, Anders Malarstig, Damiano Baldassarre, Yan Borne, Ulf de Faire, Gunnar Engström, Per Eriksson, Philippe Giral, Steve E Humphries, Sudhir Kurl, Karin Leander, Lars Lind, Anders Lindén, Nicola Orsini, Matteo Pirro, Angela Silveira, Andries J Smit, Elena Tremoli, Fabrizio Veglia, Rona J StrawbridgeBruna Gigante

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	103374
Journal	Current Research in Translational Medicine
Volume	71
Issue number	1
Early online date	2022 Dec 6
DOIs	https://doi.org/10.1016/j.retram.2022.103374
Publication status	Published - 2023

Subject classification (UKÄ)

Medical Genetics and Genomics (including Gene Therapy)

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10.1016/j.retram.2022.103374Licence: CC BY

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Velásquez, I. M., 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., ... Gigante, B. (2023). 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. https://doi.org/10.1016/j.retram.2022.103374

@article{aa96e9d7dfc64e19acc3d423fa36fafc,

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

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.",

author = "Vel{\'a}squez, {Ilais Moreno} and Anders Malarstig and Damiano Baldassarre and Yan Borne and {de Faire}, Ulf and Gunnar Engstr{\"o}m and Per Eriksson and Philippe Giral and Humphries, {Steve E} and Sudhir Kurl and Karin Leander and Lars Lind and Anders Lind{\'e}n and Nicola Orsini and Matteo Pirro and Angela Silveira and Smit, {Andries J} and Elena Tremoli and Fabrizio Veglia and Strawbridge, {Rona J} and Bruna Gigante",

year = "2023",

doi = "10.1016/j.retram.2022.103374",

language = "English",

volume = "71",

journal = "Current Research in Translational Medicine",

issn = "2452-3186",

publisher = "Elsevier",

number = "1 ",

}

Velásquez, IM, Malarstig, A, Baldassarre, D, Borne, Y, de Faire, U, Engström, G, Eriksson, P, Giral, P, Humphries, SE, Kurl, S, Leander, K, Lind, L, Lindén, A, Orsini, N, Pirro, M, Silveira, A, Smit, AJ, Tremoli, E, Veglia, F, Strawbridge, RJ & Gigante, B 2023, 'Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis', Current Research in Translational Medicine, vol. 71, no. 1 , 103374. https://doi.org/10.1016/j.retram.2022.103374

TY - JOUR

T1 - Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis

AU - Velásquez, Ilais Moreno

AU - Malarstig, Anders

AU - Baldassarre, Damiano

AU - Borne, Yan

AU - de Faire, Ulf

AU - Engström, Gunnar

AU - Eriksson, Per

AU - Giral, Philippe

AU - Humphries, Steve E

AU - Kurl, Sudhir

AU - Leander, Karin

AU - Lind, Lars

AU - Lindén, Anders

AU - Orsini, Nicola

AU - Pirro, Matteo

AU - Silveira, Angela

AU - Smit, Andries J

AU - Tremoli, Elena

AU - Veglia, Fabrizio

AU - Strawbridge, Rona J

AU - Gigante, Bruna

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1016/j.retram.2022.103374

DO - 10.1016/j.retram.2022.103374

M3 - Article

C2 - 36493747

SN - 2452-3186

VL - 71

JO - Current Research in Translational Medicine

JF - Current Research in Translational Medicine

IS - 1

M1 - 103374

ER -

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

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