Cargando…

Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study

The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential asso...

Descripción completa

Detalles Bibliográficos
Autores principales: Bonomi, Alice, Veglia, Fabrizio, Baldassarre, Damiano, Strawbridge, Rona J., Golabkesh, Zahra, Sennblad, Bengt, Leander, Karin, Smit, Andries J., Giral, Philippe, Humphries, Steve E., Tremoli, Elena, Hamsten, Anders, de Faire, Ulf, Gigante, Bruna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182533/
https://www.ncbi.nlm.nih.gov/pubmed/31932740
http://dx.doi.org/10.1038/s41435-019-0090-z
_version_ 1783526254645870592
author Bonomi, Alice
Veglia, Fabrizio
Baldassarre, Damiano
Strawbridge, Rona J.
Golabkesh, Zahra
Sennblad, Bengt
Leander, Karin
Smit, Andries J.
Giral, Philippe
Humphries, Steve E.
Tremoli, Elena
Hamsten, Anders
de Faire, Ulf
Gigante, Bruna
author_facet Bonomi, Alice
Veglia, Fabrizio
Baldassarre, Damiano
Strawbridge, Rona J.
Golabkesh, Zahra
Sennblad, Bengt
Leander, Karin
Smit, Andries J.
Giral, Philippe
Humphries, Steve E.
Tremoli, Elena
Hamsten, Anders
de Faire, Ulf
Gigante, Bruna
author_sort Bonomi, Alice
collection PubMed
description The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10(−5) was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10(−5)) and inversely associated with c-IMT (c-IMT(mean–max) β = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
format Online
Article
Text
id pubmed-7182533
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-71825332020-05-01 Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study Bonomi, Alice Veglia, Fabrizio Baldassarre, Damiano Strawbridge, Rona J. Golabkesh, Zahra Sennblad, Bengt Leander, Karin Smit, Andries J. Giral, Philippe Humphries, Steve E. Tremoli, Elena Hamsten, Anders de Faire, Ulf Gigante, Bruna Genes Immun Article The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10(−5) was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10(−5)) and inversely associated with c-IMT (c-IMT(mean–max) β = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures. Nature Publishing Group UK 2020-01-14 2020 /pmc/articles/PMC7182533/ /pubmed/31932740 http://dx.doi.org/10.1038/s41435-019-0090-z Text en © The Author(s), under exclusive licence to Springer Nature Limited 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bonomi, Alice
Veglia, Fabrizio
Baldassarre, Damiano
Strawbridge, Rona J.
Golabkesh, Zahra
Sennblad, Bengt
Leander, Karin
Smit, Andries J.
Giral, Philippe
Humphries, Steve E.
Tremoli, Elena
Hamsten, Anders
de Faire, Ulf
Gigante, Bruna
Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
title Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
title_full Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
title_fullStr Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
title_full_unstemmed Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
title_short Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
title_sort analysis of the genetic variants associated with circulating levels of sgp130. results from the improve study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182533/
https://www.ncbi.nlm.nih.gov/pubmed/31932740
http://dx.doi.org/10.1038/s41435-019-0090-z
work_keys_str_mv AT bonomialice analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT vegliafabrizio analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT baldassarredamiano analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT strawbridgeronaj analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT golabkeshzahra analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT sennbladbengt analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT leanderkarin analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT smitandriesj analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT giralphilippe analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT humphriesstevee analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT tremolielena analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT hamstenanders analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT defaireulf analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT gigantebruna analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy
AT analysisofthegeneticvariantsassociatedwithcirculatinglevelsofsgp130resultsfromtheimprovestudy