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

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Τίτλος: Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis
Συγγραφείς: Moreno Velásquez, I., 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., Strawbridge, R.J., Gigante, B.
Στοιχεία εκδότη: Elsevier
Έτος έκδοσης: 2023
Συλλογή: Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository
Θεματικοί όροι: Cardiovascular and Metabolic Diseases, Topic 3: Integrative Biomedicine
Περιγραφή: 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 (ß) 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.
Τύπος εγγράφου: article in journal/newspaper
Περιγραφή αρχείου: application/pdf; other
Γλώσσα: English
Relation: https://edoc.mdc-berlin.de/id/eprint/22950/1/22950oa.pdf; https://edoc.mdc-berlin.de/id/eprint/22950/2/22950suppl.docx; Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis. Moreno Velásquez, I., 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., Strawbridge, R.J. and Gigante, B. Current Research in Translational Medicine 71 (1): 103374. January 2023; PMID:36493747; https://doi.org/10.1016/j.retram.2022.103374
DOI: 10.1016/j.retram.2022.103374
Διαθεσιμότητα: https://edoc.mdc-berlin.de/id/eprint/22950/
https://edoc.mdc-berlin.de/22950/
https://doi.org/10.1016/j.retram.2022.103374
Rights: cc_by_4
Αριθμός Καταχώρησης: edsbas.C64EE447
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  Data: Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis
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  Data: 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&lt;0&#183;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 (&#223;) of -0&#183;006 with 95%CI (-0&#183;008- -0&#183;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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  Data: https://edoc.mdc-berlin.de/id/eprint/22950/1/22950oa.pdf; https://edoc.mdc-berlin.de/id/eprint/22950/2/22950suppl.docx; Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis. Moreno Vel&#225;squez, I., Malarstig, A., Baldassarre, D., Borne, Y., de Faire, U., Engstr&#246;m, G., Eriksson, P., Giral, P., Humphries, S.E., Kurl, S., Leander, K., Lind, L., Lind&#233;n, A., Orsini, N., Pirro, M., Silveira, A., Smit, A.J., Tremoli, E., Veglia, F., Strawbridge, R.J. and Gigante, B. Current Research in Translational Medicine 71 (1): 103374. January 2023; PMID:36493747; https://doi.org/10.1016/j.retram.2022.103374
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