Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Anderson, CD; Falcone, GJ; Phuah, CL; Radmanesh, F; Brouwers, HB; Battey, TW; Biffi, A; Peloso, GM; Liu, DJ; Ayres, AM; Goldstein, JN; Viswanathan, A; Greenberg, SM; Selim, M; Meschia, JF; Brown, DL; Worrall, BB; Silliman, SL; Tirschwell, DL; Flaherty, ML; Kraft, P; Jagiella, JM; Schmidt, H; Hansen, BM; Jimenez-Conde, J; Giralt-Steinhauer, E; Elosua, R; Cuadrado-Godia, E; Soriano, C; van Nieuwenhuizen, KM; Klijn, CJ; Rannikmae, K; Samarasekera, N; Al-Shahi Salman, R; Sudlow, CL; Deary, IJ; Morotti, A; Pezzini, A; Pera, J; Urbanik, A; Pichler, A; Enzinger, C; Norrving, B; Montaner, J; Fernandez-Cadenas, I; Delgado, P; Roquer, J; Lindgren, A; Slowik, A; Schmidt, R; Kidwell, CS; Kittner, SJ; Waddy, SP; Langefeld, CD; Abecasis, G; Willer, CJ; Kathiresan, S; Woo, D; Rosand, J; Global Lipids Genetics Consortium and International Stroke Genetics Consortium.
Genetic variants in CETP increase risk of intracerebral hemorrhage.
Ann Neurol. 2016; 80(5):730-740
Doi: 10.1002/ana.24780
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- Co-Autor*innen der Med Uni Graz
- Enzinger Christian
- Pichler Alexander
- Schmidt Helena
- Schmidt Reinhold
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- Abstract:
- 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. 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. 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 (I2 = 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 ). 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. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Cerebral Hemorrhage - genetics
- Cholesterol Ester Transfer Proteins - genetics
- Cholesterol, HDL - blood
- Cholesterol, HDL - genetics
- Female -
- Genetic Predisposition to Disease - genetics
- Genotype -
- Humans -
- Male -
- Middle Aged -
- Polymorphism, Single Nucleotide -