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

H Grallert, J Dupuis, JC Bis, Abbas Dehghan, M Barbalic, J Baumert, C Lu, NL Smith, André Uitterlinden, R Roberts, N Khuseyinova, RB Schnabel, KM Rice, Fernando Rivadeneira, RC Hoogeveen, JD Fontes, C Meisinger, JF Keaney, R Lemaitre, YS AulchenkoRS Vasan, S Ellis, SL Hazen, Cornelia Duijn, JJ Nelson, W Marz, H Schunkert, RM McPherson, HA Stirnadel-Farrant, BM Psaty, C Gieger, D Siscovick, Bert Hofman, T Illig, M Cushman, JF Yamamoto, JI Rotter, MG Larson, AFR Stewart, E Boerwinkle, JCM Witteman, RP Tracy, W Koenig, EJ Benjamin, CM Ballantyne

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Abstract

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 x 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 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.
Original languageUndefined/Unknown
Pages (from-to)238-251
Number of pages14
JournalEuropean Heart Journal
Volume33
Issue number2
DOIs
Publication statusPublished - 2012

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