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  • Laurila, Pirkka-PekkaInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland; Department of Medical Genetics, University of Helsinki, Helsinki, Finland (author)

Genomic, transcriptomic, and lipidomic profiling highlights the role of inflammation in individuals with low high-density lipoprotein cholesterol

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • Lippincott Williams & Wilkins,2013
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-63677
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-63677URI
  • https://doi.org/10.1161/ATVBAHA.112.300733DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

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

Notes

  • Funding agencies:Finnish Foundation for Cardiovascular ResearchNovo Nordisk FoundationHelsinki University Central Hospital Research FoundationEmil Aaltonen FoundationFinnish Medical FoundationBiomedicum Helsinki FoundationAarne Koskelo FoundationFinska LakaresallskapetResearch Council for the HealthAcademy of Finland 132625Paavo Nurmi Foundation
  • OBJECTIVE: Low high-density lipoprotein cholesterol (HDL-C) is associated with cardiometabolic pathologies. In this study, we investigate the biological pathways and individual genes behind low HDL-C by integrating results from 3 high-throughput data sources: adipose tissue transcriptomics, HDL lipidomics, and dense marker genotypes from Finnish individuals with low or high HDL-C (n=450).APPROACH AND RESULTS: In the pathway analysis of genetic data, we demonstrate that genetic variants within inflammatory pathways were enriched among low HDL-C associated single-nucleotide polymorphisms, and the expression of these pathways upregulated in the adipose tissue of low HDL-C subjects. The lipidomic analysis highlighted the change in HDL particle quality toward putatively more inflammatory and less vasoprotective state in subjects with low HDL-C, as evidenced by their decreased antioxidative plasmalogen contents. We show that the focal point of these inflammatory pathways seems to be the HLA region with its low HDL-associated alleles also associating with more abundant local transcript levels in adipose tissue, increased plasma vascular cell adhesion molecule 1 (VCAM1) levels, and decreased HDL particle plasmalogen contents, markers of adipose tissue inflammation, vascular inflammation, and HDL antioxidative potential, respectively. In a population-based look-up of the inflammatory pathway single-nucleotide polymorphisms in a large Finnish cohorts (n=11 211), no association of the HLA region was detected for HDL-C as quantitative trait, but with extreme HDL-C phenotypes, implying the presence of low or high HDL genes in addition to the population-genomewide association studies-identified HDL genes.CONCLUSIONS: Our study highlights the role of inflammation with a genetic component in subjects with low HDL-C and identifies novel cis-expression quantitative trait loci (cis-eQTL) variants in HLA region to be associated with low HDL-C.

Subject headings and genre

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  • Surakka, IdaInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Sarin, Antti-PekkaInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Yetukuri, LaxmanVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Hyötyläinen, Tuulia,1971-Örebro universitet,Institutionen för naturvetenskap och teknik,VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)tihn (author)
  • Söderlund, SanniDepartment of Medicine, Helsinki University Central Hospital, Helsinki, Finland (author)
  • Naukkarinen, JussiPublic Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Tang, JingVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Kettunen, JohannesInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Mirel, Daniel BProgram in Medical and Population Genetics, Broad Institute, Cambridge MA, United States (author)
  • Soronen, JarkkoPublic Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Lehtimäki, TerhoDepartment of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, Finland (author)
  • Ruokonen, AimoInstitute of Diagnostics, University of Oulu, Oulu, Finland (author)
  • Ehnholm, ChristianPublic Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Eriksson, Johan G.Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland; Folkhälsan Research Centre, Helsinki, Finland; Vasa Central Hospital, Vasa, FinlandM; Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Salomaa, VeikkoDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Jula, AnttiDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Raitakari, Olli TResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Clinical Physiology, University of Turku, Turku University Hospital, Turku, Finland (author)
  • Järvelin, Marjo-RiittaDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Institute of Health Sciences, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland (author)
  • Palotie, AarnoInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Department of Medical Genetics, University of Helsinki, Helsinki, Finland; Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Cambridge, United Kingdom; Program in Medical and Population Genetics, Broad Institute, Cambridge MA, United States (author)
  • Peltonen, Leena (author)
  • Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)moc (author)
  • Jauhiainen, MattiPublic Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland (author)
  • Taskinen, Marja-RiittaDepartment of Medicine, Helsinki University Central Hospital, Helsinki, Finland (author)
  • Ripatti, SamuliInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland; Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Cambridge, United Kingdom (author)
  • Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland; Department of Medical Genetics, University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland (creator_code:org_t)

Related titles

  • In:Arteriosclerosis, Thrombosis and Vascular Biology: Lippincott Williams & Wilkins33:4, s. 847-8571079-56421524-4636

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