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Sökning: onr:"swepub:oai:DiVA.org:oru-63677" > Genomic, transcript...

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

Laurila, Pirkka-Pekka, (författare)
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, Finland
Surakka, Ida, (författare)
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
Sarin, Antti-Pekka, (författare)
Institute 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, Laxman, (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Hyötyläinen, Tuulia, 1971- (författare)
Örebro universitet, Institutionen för naturvetenskap och teknik, VTT Technical Research Centre of Finland, Espoo, Finland
Söderlund, Sanni, (författare)
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
Naukkarinen, Jussi, (författare)
Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
Tang, Jing, (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Kettunen, Johannes, (författare)
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland; Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
Mirel, Daniel B, (författare)
Program in Medical and Population Genetics, Broad Institute, Cambridge MA, United States
Soronen, Jarkko, (författare)
Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
Lehtimäki, Terho, (författare)
Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, Finland
Ruokonen, Aimo, (författare)
Institute of Diagnostics, University of Oulu, Oulu, Finland
Ehnholm, Christian, (författare)
Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
Eriksson, Johan G., (författare)
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
Salomaa, Veikko, (författare)
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
Jula, Antti, (författare)
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
Raitakari, Olli T, (författare)
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Clinical Physiology, University of Turku, Turku University Hospital, Turku, Finland
Järvelin, Marjo-Riitta, (författare)
Department 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
Palotie, Aarno, (författare)
Institute 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
Peltonen, Leena (författare)
Oresic, Matej, 1967- (författare)
Örebro universitet, Institutionen för medicinska vetenskaper, VTT Technical Research Centre of Finland, Espoo, Finland
Jauhiainen, Matti, (författare)
Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
Taskinen, Marja-Riitta, (författare)
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
Ripatti, Samuli, (författare)
Institute 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
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Örebro universitet Institutionen för naturvetenskap och teknik. (creator_code:org_t)
Örebro universitet Institutionen för medicinska vetenskaper. (creator_code:org_t)
2013
Engelska.
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - Lippincott Williams & Wilkins. - 1079-5642. ; 33:4, s. 847-857
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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