Ilais Moreno Velásquez1, Jitender Kumar2, Harry Björkbacka3, Jan Nilsson3, Angela Silveira4, Karin Leander5, Anita Berglund5, Rona J Strawbridge4, Johan Ärnlöv6, Olle Melander7, Peter Almgren8, Lars Lind9, Anders Hamsten4, Ulf de Faire10, Bruna Gigante11. 1. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: ilais.moreno.velasquez@ki.se. 2. Dept of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. 3. Experimental Cardiovascular Research Unit, Dept of Clinical Sciences Malmö, Lund University, Malmö, Sweden. 4. Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 5. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 6. 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. 7. Hypertension and Cardiovascular Disease, Dept of Clinical Sciences, Lund University, Malmö, Sweden; Centre of Emergency Medicine, Skåne University Hospital, Malmö, Sweden. 8. Hypertension and Cardiovascular Disease, Dept of Clinical Sciences, Lund University, Malmö, Sweden. 9. Dept of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden. 10. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Cardiology, Karolinska University Hospital, Stockholm, Sweden. 11. 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.
Abstract
UNLABELLED: 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.
UNLABELLED: 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.
Authors: S J Glisovic; Y D Pastore; V Gagne; M Plesa; C Laverdière; J M Leclerc; D Sinnett; M Krajinovic Journal: Pharmacogenomics J Date: 2017-05-23 Impact factor: 3.550
Authors: Bashira A Charles; Matthew M Hsieh; Adebowale A Adeyemo; Daniel Shriner; Edward Ramos; Kyung Chin; Kshitij Srivastava; Neil A Zakai; Mary Cushman; Leslie A McClure; Virginia Howard; Willy A Flegel; Charles N Rotimi; Griffin P Rodgers Journal: PLoS One Date: 2018-03-29 Impact factor: 3.240
Authors: María Ángeles Jiménez-Sousa; Ana Zaida Gómez-Moreno; Daniel Pineda-Tenor; Juan José Sánchez-Ruano; Tomas Artaza-Varasa; María Martin-Vicente; Amanda Fernández-Rodríguez; Isidoro Martínez; Salvador Resino Journal: Biomolecules Date: 2019-04-09