Duffy antigen receptor genetic variant and the association with Interleukin 8 levels.

Research output: Contribution to journalArticle

Abstract

The aim of this study is to identify loci associated with circulating levels of Interleukin 8 (IL8). We investigated the associations of 121,445 single nucleotide polymorphisms (SNPs) from the Illumina 200K CardioMetabochip with IL8 levels in 1077 controls from the Stockholm Heart Epidemiology Program (SHEEP) study, using linear regression under an additive model of inheritance. Five SNPs (rs12075A/G, rs13179413C/T, rs6907989T/A, rs9352745A/C, rs1779553T/C) reached the pre-defined threshold of genome-wide significance (p<1.0×10(-5)) and were tested for in silico replication in three independent populations, derived from the PIVUS, MDC-CC and SCARF studies. IL8 was measured in serum (SHEEP, PIVUS) and plasma (MDC-CC, SCARF). The strongest association was found with the SNP rs12075 A/G, Asp42Gly (p=1.6×10(-6)), mapping to the Duffy antigen receptor for chemokines (DARC) gene on chromosome 1. The minor allele G was associated with 15.6% and 10.4% reduction in serum IL8 per copy of the allele in SHEEP and PIVUS studies respectively. No association was observed between rs12075 and plasma IL8. Conclusion: rs12075 was associated with serum levels but not with plasma levels of IL8. It is likely that serum IL8 represents the combination of levels of circulating plasma IL8 and additional chemokine liberated from the erythrocyte DARC reservoir due to clotting. These findings highlight the importance of understanding IL8 as a biomarker in cardiometabolic diseases.

Details

Authors
  • Ilais Moreno Velásquez
  • Jitender Kumar
  • Harry Björkbacka
  • Jan Nilsson
  • Angela Silveira
  • Karin Leander
  • Anita Berglund
  • Rona J Strawbridge
  • Johan Ärnlöv
  • Olle Melander
  • Peter Almgren
  • Lars Lind
  • Anders Hamsten
  • Ulf de Faire
  • Bruna Gigante
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)178-184
JournalCytokine
Volume72
Issue number2
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes