Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies

Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association...

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Published in:European heart journal Vol. 33; no. 2; p. 238
Main Authors: Grallert, Harald, Dupuis, Josée, Bis, Joshua C, Dehghan, Abbas, Barbalic, Maja, Baumert, Jens, Lu, Chen, Smith, Nicholas L, Uitterlinden, André G, Roberts, Robert, Khuseyinova, Natalie, Schnabel, Renate B, Rice, Kenneth M, Rivadeneira, Fernando, Hoogeveen, Ron C, Fontes, João Daniel, Meisinger, Christa, Keaney, Jr, John F, Lemaitre, Rozenn, Aulchenko, Yurii S, Vasan, Ramachandran S, Ellis, Stephen, Hazen, Stanley L, van Duijn, Cornelia M, Nelson, Jeanenne J, März, Winfried, Schunkert, Heribert, McPherson, Ruth M, Stirnadel-Farrant, Heide A, Psaty, Bruce M, Gieger, Christian, Siscovick, David, Hofman, Albert, Illig, Thomas, Cushman, Mary, Yamamoto, Jennifer F, Rotter, Jerome I, Larson, Martin G, Stewart, Alexandre F R, Boerwinkle, Eric, Witteman, Jacqueline C M, Tracy, Russell P, Koenig, Wolfgang, Benjamin, Emelia J, Ballantyne, Christie M
Format: Journal Article
Language:English
Published: England 01.01.2012
Subjects:
1-Alkyl-2-acetylglycerophosphocholine Esterase
Aged
Coronary Artery Disease - genetics
Coronary Disease - genetics
Female
Genetic Loci - genetics
Genome-Wide Association Study
Humans
Male
Middle Aged
Phospholipases A2 - genetics
Polymorphism, Single Nucleotide - genetics
ISSN:1522-9645, 1522-9645
Online Access:Get more information
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Summary:Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 × 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 × 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study. Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.
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ISSN:1522-9645
1522-9645
DOI:10.1093/eurheartj/ehr372