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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 ...
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Lippincott Williams & Wilkins,2013
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printrdacarrier
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LIBRIS-ID:oai:DiVA.org:oru-63677
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-63677URI
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https://doi.org/10.1161/ATVBAHA.112.300733DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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
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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.
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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
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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
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Yetukuri, LaxmanVTT Technical Research Centre of Finland, Espoo, Finland
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Hyötyläinen, Tuulia,1971-Örebro universitet,Institutionen för naturvetenskap och teknik,VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)tihn
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Söderlund, SanniDepartment of Medicine, Helsinki University Central Hospital, Helsinki, Finland
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Naukkarinen, JussiPublic Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
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Tang, JingVTT Technical Research Centre of Finland, Espoo, Finland
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Kettunen, JohannesInstitute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
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Mirel, Daniel BProgram in Medical and Population Genetics, Broad Institute, Cambridge MA, United States
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Soronen, JarkkoPublic Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
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Lehtimäki, TerhoDepartment of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, Finland
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Ruokonen, AimoInstitute of Diagnostics, University of Oulu, Oulu, Finland
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Ehnholm, ChristianPublic Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
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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
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Salomaa, VeikkoDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
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Jula, AnttiDepartment of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
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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
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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
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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
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Peltonen, Leena
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Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)moc
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Jauhiainen, MattiPublic Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
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Taskinen, Marja-RiittaDepartment of Medicine, Helsinki University Central Hospital, Helsinki, Finland
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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)
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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)
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In:Arteriosclerosis, Thrombosis and Vascular Biology: Lippincott Williams & Wilkins33:4, s. 847-8571079-56421524-4636
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Laurila, Pirkka- ...
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Surakka, Ida
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Sarin, Antti-Pek ...
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Yetukuri, Laxman
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Hyötyläinen, Tuu ...
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Söderlund, Sanni
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Naukkarinen, Jus ...
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Tang, Jing
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Mirel, Daniel B
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Soronen, Jarkko
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Lehtimäki, Terho
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Ruokonen, Aimo
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Ehnholm, Christi ...
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Eriksson, Johan ...
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Salomaa, Veikko
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Jula, Antti
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Raitakari, Olli ...
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Järvelin, Marjo- ...
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Palotie, Aarno
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Peltonen, Leena
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Oresic, Matej, 1 ...
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