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  • Anderson, Christopher D.Broad Institute (author)

Genetic variants in CETP increase risk of intracerebral hemorrhage

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-10-19
  • Wiley,2016
  • 11 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:143e4406-326c-4bd4-83e4-180d889d76e7
  • https://lup.lub.lu.se/record/143e4406-326c-4bd4-83e4-180d889d76e7URI
  • https://doi.org/10.1002/ana.24780DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10(-4) ) with no heterogeneity across studies (I(2) = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10(-6) ).INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Falcone, Guido J.Broad Institute (author)
  • Phuah, Chia-LingBroad Institute (author)
  • Radmanesh, FaridBroad Institute (author)
  • Brouwers, H BartBroad Institute (author)
  • Battey, Thomas W KBroad Institute (author)
  • Biffi, AlessandroBroad Institute (author)
  • Peloso, Gina M.Broad Institute (author)
  • Liu, Dajiang JPennsylvania State University College of Medicine (author)
  • Ayres, Alison M.Massachusetts General Hospital (author)
  • Goldstein, Joshua N. (author)
  • Viswanathan, Anand (author)
  • Greenberg, Steven M. (author)
  • Selim, Magdy (author)
  • Meschia, James F. (author)
  • Brown, Devin L. (author)
  • Worrall, Bradford (author)
  • Silliman, Scott L. (author)
  • Tirschwell, David L. (author)
  • Flaherty, Matthew L. (author)
  • Kraft, Peter (author)
  • Jagiella, Jeremiasz M. (author)
  • Schmidt, Helena (author)
  • Hansen, Björn MLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-bhe (author)
  • Jimenez-Conde, Jordi (author)
  • Giralt-Steinhauer, Eva (author)
  • Elosua, Roberto (author)
  • Cuadrado-Godia, Elisa (author)
  • Soriano, Carolina (author)
  • van Nieuwenhuizen, Koen M (author)
  • Klijn, Catharina J. M. (author)
  • Rannikmae, Kristiina (author)
  • Samarasekera, Neshika (author)
  • Al-Shahi Salman, Rustam (author)
  • Sudlow, Catherine L (author)
  • Deary, Ian J (author)
  • Morotti, Andrea (author)
  • Pezzini, Alessandro (author)
  • Pera, Joanna (author)
  • Urbanik, Andrzej (author)
  • Pichler, Alexander (author)
  • Enzinger, Christian (author)
  • Norrving, BoLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)neur-bno (author)
  • Montaner, Joan (author)
  • Fernandez-Cadenas, Israel (author)
  • Delgado, Pilar (author)
  • Roquer, Jaume (author)
  • Lindgren, ArneLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)neur-ali (author)
  • Slowik, Agnieszka (author)
  • Schmidt, Reinhold (author)
  • Broad InstitutePennsylvania State University College of Medicine (creator_code:org_t)
  • Global Lipids Genetics Consortium
  • International Stroke Genetics Consortium

Related titles

  • In:Annals of Neurology: Wiley80:5, s. 730-7401531-82490364-5134

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