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Duffy antigen receptor genetic variant and the association with Interleukin 8 levels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2015 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 72, no 2, 178-184 p.Article in journal (Refereed) Published
Abstract [en]

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 predefined threshold of genome-wide significance (p < 1.0 x 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 x 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 ILS as a biomarker in cardiometabolic diseases. 

Place, publisher, year, edition, pages
2015. Vol. 72, no 2, 178-184 p.
Keyword [en]
Interleukin 8, Duffy antigen receptor for chemokine, Genetic variants
National Category
Cell and Molecular Biology
URN: urn:nbn:se:uu:diva-258821DOI: 10.1016/j.cyto.2014.12.019ISI: 000351656500009OAI: oai:DiVA.org:uu-258821DiVA: diva2:842937
Available from: 2015-07-23 Created: 2015-07-20 Last updated: 2015-07-23Bibliographically approved

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Kumar, JitenderÄrnlöv, JohanLind, Lars
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Molecular epidemiologyScience for Life Laboratory, SciLifeLabCardiovascular epidemiology
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