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  • Froguel, Philippe (author)

A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012-03-05
  • Public Library of Science (PLoS),2012

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/273563
  • https://gup.ub.gu.se/publication/273563URI
  • https://doi.org/10.1371/journal.pone.0032327DOI

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  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far. We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism (SNP), rs2000999 located in the Haptoglobin gene (HP) as a strong genetic predictor of circulating Haptoglobin levels (P overall = 8.1×10 -59), explaining 45.4% of its genetic variability (11.8% of Hp global variance). The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (β = 0.23±0.08, P = 0.007). Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children (P total cholesterol = 0.002 and P LDL = 0.0008). Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact. © 2012 Froguel et al.

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  • Ndiaye, Ndeye Coumba (author)
  • Bonnefond, Amélie (author)
  • Bouatia-Naji, Nabila (author)
  • Dechaume, Aurélie (author)
  • Siest, Gérard (author)
  • Herbeth, Bernard (author)
  • Falchi, Mario (author)
  • Bottolo, Leonardo (author)
  • Guéant-Rodriguez, Rosa Maria (author)
  • Lecoeur, Cécile (author)
  • Langlois, Michel R. (author)
  • Labrune, Yann (author)
  • Ruokonen, Aimo (author)
  • El Shamieh, Said (author)
  • Stathopoulou, Maria G. (author)
  • Morandi, Anita (author)
  • Maffeis, Claudio (author)
  • Meyre, David (author)
  • Delanghe, Joris R. (author)
  • Jacobson, Peter,1962Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xjacop (author)
  • Sjöström, LarsGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xsjosl (author)
  • Carlsson, Lena M S,1957Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcarle (author)
  • Walley, Andrew (author)
  • Elliott, PaulGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine (author)
  • Jarvelin, Marjo Riita (author)
  • Dedoussis, George V. (author)
  • Visvikis-Siest, Sophie (author)
  • Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin (creator_code:org_t)

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  • In:PLoS ONE: Public Library of Science (PLoS)71932-6203

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