title: Duffy antigen receptor genetic variant and the association with Interleukin 8 levels.
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.
  
  
  CONCLUSIONS
  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.
authors: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: ilais.moreno.velasquez@ki.se.
authors: Ilais
authors: I
authors: Moreno Velásquez
authors: Dept of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Jitender
authors: J
authors: Kumar
authors: Experimental Cardiovascular Research Unit, Dept of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors: Harry
authors: H
authors: Björkbacka
authors: Experimental Cardiovascular Research Unit, Dept of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors: Jan
authors: J
authors: Nilsson
authors: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors: Angela
authors: A
authors: Silveira
authors: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Karin
authors: K
authors: Leander
authors: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Anita
authors: A
authors: Berglund
authors: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors: Rona J
authors: RJ
authors: Strawbridge
authors: Dept of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
authors: Johan
authors: J
authors: Ärnlöv
authors: Hypertension and Cardiovascular Disease, Dept of Clinical Sciences, Lund University, Malmö, Sweden; Centre of Emergency Medicine, Skåne University Hospital, Malmö, Sweden.
authors: Olle
authors: O
authors: Melander
authors: Hypertension and Cardiovascular Disease, Dept of Clinical Sciences, Lund University, Malmö, Sweden.
authors: Peter
authors: P
authors: Almgren
authors: Dept of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
authors: Lars
authors: L
authors: Lind
authors: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors: Anders
authors: A
authors: Hamsten
authors: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors: Ulf
authors: U
authors: de Faire
authors: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Cardiovascular Medicine, Dept of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
authors: Bruna
authors: B
authors: Gigante
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004375:Duffy Blood-Group System / Q000235:genetics*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011946:Receptors, Antigen; D011956:Receptors, Cell Surface / Q000235:genetics*; D013997:Time Factors
chemical_list: C473745:ACKR1 protein, human; C508606:CXCL8 protein, human; D004375:Duffy Blood-Group System; D016209:Interleukin-8; D011946:Receptors, Antigen; D011956:Receptors, Cell Surface
keywords: Duffy antigen receptor for chemokine; Genetic variants; Interleukin 8