PuSH - Publication Server of Helmholtz Zentrum München

Grallert, H. ; Dupuis, J.* ; Bis, J.C.* ; Dehghan, A.* ; Barbalic, M.* ; Baumert, J.J. ; Lu, C.* ; Smith, N.L.* ; Uitterlinden, A.G.* ; Roberts, R.* ; Khuseyinova, N.* ; Schnabel, R.B.* ; Rice, K.M.* ; Rivadeneira, F.* ; Hoogeveen, R.C.* ; Fontes, J.D.* ; Meisinger, C. ; Keaney, J.F.* ; Lemaitre, R.* ; Aulchenko, Y.S.* ; Vasan, R.S.* ; Ellis, S.* ; Hazen, S.L.* ; van Duijn, C.M.* ; Nelson, J.J.* ; Marz, W.* ; Schunkert, H.* ; McPherson, R.M.* ; Stirnadel-Farrant, H.A.* ; Psaty, B.M.* ; Gieger, C. ; Siscovick, D.* ; Hofman, A.* ; Illig, T. ; Cushman, M.* ; Yamamoto, J.F.* ; Rotter, J.I.* ; Larson, M.G.* ; Stewart, A.F.* ; Boerwinkle, E.* ; Witteman, J.C.* ; Tracy, R.P.* ; Koenig, W.* ; Benjamin, E.J.* ; Ballantyne, C.M.*

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.

Eur. Heart J. 33, 238-251 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide association; Inflammation; Lipoprotein-associated phospholipase A2
ISSN (print) / ISBN 0195-668X
e-ISSN 1522-9645
Journal European Heart Journal
Quellenangaben Volume: 33, Issue: 2, Pages: 238-251 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
Institute of Genetic Epidemiology (IGE)