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
N1 - Funding Information:
Role of the funding source: The study was supported by the Strategic Research Area in Epidemiology (SFO) at KI, Apotekare Hedbergs fond and ALF (FoUI 2021 960053) (to BG). IMV was supported by the Sistema Nacional de Investigación (SNI, SENACYT, Panama). AL was supported by the Swedish Medical Research Council (#2016-01653) and the Heart-Lung Foundation (#2018-0315). Representatives for these funding sources were not involved in the design of the study, collection, analysis and interpretation of data, manuscript draft, or decision to submit the article for publication. The UK Biobank was established by the Wellcome Trust, Medical Research Council, Department of Health, Scottish Government and Northwest Regional Development Agency. UK Biobank has also had funding from the Welsh Assembly Government and the British Heart Foundation. Data collection was funded by UK Biobank. This project was completed using UK Biobank applications 6533 (PI. DJS) and 1755 (PI. JPP). RJS is supported by a University of Glasgow LKAS fellowship and a UKRI Innovation-HDR-UK Fellowship (MR/S003061/1).
Publisher Copyright:
© 2022 The Author(s)
PY - 2023/1/1
Y1 - 2023/1/1
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 MDC–CC (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 MDC–CC (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.
KW - Carotid intima media thickness
KW - Chemokines
KW - Cohort studies
KW - Genetic association studies
KW - Subclinical atherosclerosis
U2 - 10.1016/j.retram.2022.103374
DO - 10.1016/j.retram.2022.103374
M3 - Article
C2 - 36493747
AN - SCOPUS:85143883824
SN - 2452-3186
VL - 71
JO - Current Research in Translational Medicine
JF - Current Research in Translational Medicine
IS - 1
M1 - 103374
ER -