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

on behalf of the IMPROVE study group

Research output: Contribution to journalArticle

Abstract

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-IMTmean–maxβ = −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.

Original languageEnglish
JournalGenes and Immunity
DOIs
Publication statusAccepted/In press - Jan 1 2020

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Cytokine Receptor gp130
Single Nucleotide Polymorphism
Atherosclerosis
Chromosomes, Human, Pair 14
Carotid Intima-Media Thickness
Genetic Loci
Multicenter Studies
Linear Models
Interleukin-6

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

Cite this

Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study. / on behalf of the IMPROVE study group.

In: Genes and Immunity, 01.01.2020.

Research output: Contribution to journalArticle

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abstract = "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-IMTmean–maxβ = −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.",
author = "{on behalf of the IMPROVE study group} and Alice Bonomi and Fabrizio Veglia and Damiano Baldassarre and Strawbridge, {Rona J.} and Zahra Golabkesh and Bengt Sennblad and Karin Leander and Smit, {Andries J.} and Philippe Giral and Humphries, {Steve E.} and Elena Tremoli and Anders Hamsten and {de Faire}, Ulf and Bruna Gigante and Sirtori, {C. R.} and S. Castelnuovo and L. Calabresi and M. Amato and B. Frigerio and A. Ravani and D. Sansaro and D. Coggi and Tedesco, {C. C.} and P. Eriksson and A. Silveira and F. Laguzzi and J. Cooper and J. Acharya and K. Huttunen and E. Rauramaa and H. Pekkarinen and Penttila, {I. M.} and J. T{\"o}rr{\"o}nen and R. Rauramaa and {van Gessel}, {A. I.} and {van Roon}, {A. M.} and Teune, {G. C.} and Kuipers, {W. D.} and M. Bruin and A. Nicolai and P. Haarsma-Jorritsma and Mulder, {D. J.} and Bilo, {H. J.G.} and Smeets, {G. H.} and Beaudeux, {J. L.} and Kahn, {J. F.} and V. Carreau and A. Kontush and J. Karppi and T. Nurmi",
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AU - Veglia, Fabrizio

AU - Baldassarre, Damiano

AU - Strawbridge, Rona J.

AU - Golabkesh, Zahra

AU - Sennblad, Bengt

AU - Leander, Karin

AU - Smit, Andries J.

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AU - Humphries, Steve E.

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AU - Castelnuovo, S.

AU - Calabresi, L.

AU - Amato, M.

AU - Frigerio, B.

AU - Ravani, A.

AU - Sansaro, D.

AU - Coggi, D.

AU - Tedesco, C. C.

AU - Eriksson, P.

AU - Silveira, A.

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AU - Cooper, J.

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AU - Bruin, M.

AU - Nicolai, A.

AU - Haarsma-Jorritsma, P.

AU - Mulder, D. J.

AU - Bilo, H. J.G.

AU - Smeets, G. H.

AU - Beaudeux, J. L.

AU - Kahn, J. F.

AU - Carreau, V.

AU - Kontush, A.

AU - Karppi, J.

AU - Nurmi, T.

PY - 2020/1/1

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N2 - 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-IMTmean–maxβ = −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.

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