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Mäkelä, K.M.* ; Seppälä, I.* ; Hernesniemi, J.A.* ; Lyytikäinen, L.-P.* ; Oksala, N.* ; Kleber, M.E.* ; Scharnagl, H.* ; Grammer, T.B.* ; Baumert, J.J. ; Thorand, B. ; Jula, A.* ; Hutri-Kähönen, N.* ; Juonala, M.* ; Laitinen, T.* ; Laaksonen, R.* ; Karhunen, P.J.* ; Nikus, K.C.* ; Nieminen, T.* ; Laurikka, J.* ; Kuukasjärvi, P.* ; Tarkka, M.* ; Viik, J.* ; Klopp, N. ; Illig, T. ; Kettunen, J.* ; Ahotupa, M.* ; Viikari, J.S.A.* ; Kähönen, M.* ; Raitakari, O.T.* ; Karakas, M.* ; Koenig, W.* ; Boehm, B.O.* ; Winkelmann, B.R.* ; Marz, W.* ; Lehtimäki, T.*

Genome-wide association study pinpoints a new functional apolipoprotein B variant influencing oxidized low-density lipoprotein levels but not cardiovascular events: AtheroRemo Consortium.

Circ. Cardiovasc. Genet. 6, 73-81 (2013)
Verlagsversion DOI
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Background-Oxidized low-density lipoprotein may be a key factor in the development of atherosclerosis. We performed a genome-wide association study on oxidized low-density lipoprotein and tested the impact of associated single-nucleotide polymorphisms (SNPs) on the risk factors of atherosclerosis and cardiovascular events. Methods and Results-A discovery genome-wide association study was performed on a population of young healthy white individuals (N=2080), and the SNPs associated with a P<5x10(-8) were replicated in 2 independent samples (A: N=2912; B: N=1326). Associations with cardiovascular endpoints were also assessed with 2 additional clinical cohorts (C: N=1118; and D: N=808). We found 328 SNPs associated with oxidized low-density lipoprotein. The genetic variant rs676210 (Pro2739Leu) in apolipoprotein B was the proxy SNP behind all associations (P=4.3x10(-136), effect size=13.2 U/L per allele). This association was replicated in the 2 independent samples (A and B, P=2.5x10(-47) and 1.1x10(-11), effect sizes=10.3 U/L and 7.8 U/L, respectively). In the meta-analyses of cohorts A, C, and D (excluding cohort B without angiographic data), the top SNP did not associate significantly with the age of onset of angiographically verified coronary artery disease (hazard ratio=1.00 [0.94-1.06] per allele), 3-vessel coronary artery disease (hazard ratio=1.03 [0.94-1.13]), or myocardial infarction (hazard ratio=1.04 [0.96-1.12]). Conclusions-This novel genetic marker is an important factor regulating oxidized low-density lipoprotein levels but not a major genetic factor for the studied cardiovascular endpoints.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Atherosclerosis ; Coronary Artery Disease ; Genome-wide Association Study ; Lipoproteins ; Oxidative Stress; Coronary-artery-disease ; Risk ; Population ; Cohort ; Atherosclerosis ; Oxidation ; Genotype ; Design ; Lipids
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Quellenangaben Band: 6, Heft: 1, Seiten: 73-81 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Hagerstown, Md
Begutachtungsstatus Peer reviewed