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

Moreno Velásquez, Ilais; Kumar, Jitender; Björkbacka, Harry LU ; Nilsson, Jan LU ; Silveira, Angela; Leander, Karin; Berglund, Anita; Strawbridge, Rona J; Ärnlöv, Johan and Melander, Olle LU , et al. (2015) In Cytokine 72(2). p.178-184
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... (More)
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. (Less)
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Contribution to journal
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published
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Cytokine
volume
72
issue
2
pages
178 - 184
publisher
Academic Press
external identifiers
  • pmid:25647274
  • wos:000351656500009
  • scopus:84921985624
ISSN
1096-0023
DOI
10.1016/j.cyto.2014.12.019
language
English
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yes
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1fd474cf-5981-4d7a-accd-9f5becb5c849 (old id 5145556)
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http://www.ncbi.nlm.nih.gov/pubmed/25647274?dopt=Abstract
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2015-03-03 20:41:52
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2017-01-01 03:26:33
@article{1fd474cf-5981-4d7a-accd-9f5becb5c849,
  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&lt;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.},
  author       = {Moreno Velásquez, Ilais and Kumar, Jitender and Björkbacka, Harry and Nilsson, Jan and Silveira, Angela and Leander, Karin and Berglund, Anita and Strawbridge, Rona J and Ärnlöv, Johan and Melander, Olle and Almgren, Peter and Lind, Lars and Hamsten, Anders and de Faire, Ulf and Gigante, Bruna},
  issn         = {1096-0023},
  language     = {eng},
  number       = {2},
  pages        = {178--184},
  publisher    = {Academic Press},
  series       = {Cytokine},
  title        = {Duffy antigen receptor genetic variant and the association with Interleukin 8 levels.},
  url          = {http://dx.doi.org/10.1016/j.cyto.2014.12.019},
  volume       = {72},
  year         = {2015},
}