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

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine Pub Date : 2023-01-01 DOI:10.1016/j.retram.2022.103374

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

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引用次数: 0

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.

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血浆IL-8对颈动脉内膜中膜厚度(亚临床动脉粥样硬化的量度)影响的原因分析

背景我们研究了IL-8对颈动脉内膜-中层厚度（c-IMT）的因果关系，c-IMT是亚临床动脉粥样硬化的一种衡量指标。方法改良是一项多中心的欧洲研究（n=3711）。通过分位数回归估计血浆IL-8与c-IMT（mm）的相关性。使用Illumina CardioMetabo和Immuno芯片进行基因分型。在三项独立研究中尝试了复制，并使用随机模型进行了荟萃分析。结果在PROVEE中，在多变量分析中，血浆IL-8的每单位增加都与c-IMT测量中值的增加有关（均p＜0.03）。线性回归确定rs117518778和rs8057084与IL-8水平和c-IMT测量相关。这两个SNPs结合在IL-8增加的遗传风险中，在PROVEE和英国生物库中显示IL-8对c-IMT的因果关系（n=22179）。在PIVUS（n=1016）和MDCC（n=6103）中证实了IL-8对c-IMT测量的影响。在PIVUS和UK Biobank中证实了rs8057084与c-IMT的相关性，合并估计效应（β）为-0.006，置信区间为95%（-0.008--0.003）。结论与血浆IL-8相关的基因变异也与c-IMT相关。然而，我们无法推断这种关联的因果关系，因为这些变体位于IL8基因座之外。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Research in Translational Medicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

7.00

自引率

4.90%

发文量

审稿时长

45 days

期刊介绍： Current Research in Translational Medicine is a peer-reviewed journal, publishing worldwide clinical and basic research in the field of hematology, immunology, infectiology, hematopoietic cell transplantation, and cellular and gene therapy. The journal considers for publication English-language editorials, original articles, reviews, and short reports including case-reports. Contributions are intended to draw attention to experimental medicine and translational research. Current Research in Translational Medicine periodically publishes thematic issues and is indexed in all major international databases (2017 Impact Factor is 1.9). Core areas covered in Current Research in Translational Medicine are: Hematology, Immunology, Infectiology, Hematopoietic, Cell Transplantation, Cellular and Gene Therapy.