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

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-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.

• Authors: Alice Bonomi, Fabrizio Veglia, Damiano Baldassarre, Rona J Strawbridge, Zahra Golabkesh, Bengt Sennblad, Karin Leander, Andries J Smit, Philippe Giral, Steve E Humphries, Elena Tremoli, Anders Hamsten, Ulf de Faire, Bruna Gigante, on behalf of the IMPROVE study group
• Journal: Genes and immunity (Genes Immun) Vol. 21 Issue 2 Pg. 100-108 (02 2020) ISSN: 1476-5470 [Electronic] England
• PMID: 31932740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• IL6 protein, human
• Interleukin-6
• Cytokine Receptor gp130

Topics

• Aged
• Atherosclerosis (blood, genetics, pathology)
• Biomarkers (blood)
• Carotid Intima-Media Thickness
• Cytokine Receptor gp130 (blood, genetics)
• Female
• Gene Frequency
• Genetic Loci
• Genetic Predisposition to Disease
• Genetic Variation
• Humans
• Interleukin-6 (blood, genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Factors