Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study - Sorbonne Université Access content directly
Journal Articles Genes and Immunity Year : 2020

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

Alice Bonomi
  • Function : Author
Fabrizio Veglia
  • Function : Author
Damiano Baldassarre
  • Function : Author
Rona Strawbridge
Zahra Golabkesh
  • Function : Author
Bengt Sennblad
Karin Leander
  • Function : Author
Andries Smit
  • Function : Author
Philippe Giral
  • Function : Author
Steve Humphries
  • Function : Author
Elena Tremoli
  • Function : Author
Anders Hamsten
  • Function : Author
Ulf de Faire
  • Function : Author
Bruna Gigante

Abstract

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-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.

Dates and versions

hal-03998903 , version 1 (21-02-2023)

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Cite

Alice Bonomi, Fabrizio Veglia, Damiano Baldassarre, Rona Strawbridge, Zahra Golabkesh, et al.. Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study. Genes and Immunity, 2020, 21 (2), pp.100-108. ⟨10.1038/s41435-019-0090-z⟩. ⟨hal-03998903⟩
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