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SHR Neuro Cancer Cardio Lipid Metab Microb
Makela, KM; Seppala, I; Hernesniemi, JA; Lyytikainen, LP; Oksala, N; Kleber, ME; Scharnagl, H; Grammer, TB; Baumert, J; Thorand, B; Jula, A; Hutri-Kahonen, N; Juonala, M; Laitinen, T; Laaksonen, R; Karhunen, PJ; Nikus, KC; Nieminen, T; Laurikka, J; Kuukasjarvi, P; Tarkka, M; Viik, J; Klopp, N; Illig, T; Kettunen, J; Ahotupa, M; Viikari, JSA; Kahonen, M; Raitakari, OT; Karakas, M; Koenig, W; Boehm, BO; Winkelmann, BR; Marz, W; Lehtimaki, 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. 2013; 6(1):73-81
Doi: 10.1161/CIRCGENETICS.112.964965
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- Co-authors Med Uni Graz
- März Winfried
- Scharnagl Hubert
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- Abstract:
- 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. (Circ Cardiovasc Genet. 2013;6:73-81.)
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Aged, 80 and over -
- Apolipoproteins B - genetics Apolipoproteins B - metabolism
- Atherosclerosis - blood Atherosclerosis - genetics
- Cardiovascular Diseases - blood Cardiovascular Diseases - genetics
- Cohort Studies -
- Female -
- Genetic Predisposition to Disease -
- Genetic Variation -
- Genome-Wide Association Study -
- Humans -
- Lipoproteins, LDL - blood
- Male -
- Middle Aged -
- Mutation, Missense -
- Polymorphism, Single Nucleotide -
- Find related publications in this database (Keywords)
- atherosclerosis
- coronary artery disease
- genome-wide association study
- lipoproteins
- oxidative stress