학술논문
Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis
Document Type
Author
Velásquez, Ilais Moreno; Malarstig, Anders; Baldassarre, Damiano; Borne, Yan; de Faire, Ulf; Engström, Gunnar; Eriksson, Per; Giral, Philippe; Humphries, Steve E; Kurl, Sudhir; Leander, Karin; Lind, Lars; Lindén, Anders; Orsini, Nicola; Pirro, Matteo; Silveira, Angela; Smit, Andries J; Tremoli, Elena; Veglia, Fabrizio; Strawbridge, Rona J; Gigante, Bruna
Source
Current Research in Translational Medicine EXODIAB: Excellence of Diabetes Research in Sweden EpiHealth: Epidemiology for Health. 71(1)
Subject
Language
English
ISSN
2452-3186
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.