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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.
Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
| Title | 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. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Grallert, H, Dupuis, J, Bis, JC, Dehghan, A, Barbalic, M, Baumert, J, Lu, C, Smith, NL, Uitterlinden, AG, Roberts, R, Khuseyinova, N, Schnabel, RB, Rice, KM, Rivadeneira, F, Hoogeveen, RC, Fontes, JDaniel, Meisinger, C, Keaney, JF, Lemaitre, R, Aulchenko, YS, Vasan, RS, Ellis, S, Hazen, SL, van Duijn, CM, Nelson, JJ, März, W, Schunkert, H, McPherson, RM, Stirnadel-Farrant, HA, Psaty, BM, Gieger, C, Siscovick, D, Hofman, A, Illig, T, Cushman, M, Yamamoto, JF, Rotter, JI, Larson, MG, Stewart, AFR, Boerwinkle, E, Witteman, JCM, Tracy, RP, Koenig, W, Benjamin, EJ, Ballantyne, CM |
| Journal | Eur Heart J |
| Volume | 33 |
| Issue | 2 |
| Pagination | 238-51 |
| Date Published | 2012 Jan |
| ISSN | 1522-9645 |
| Keywords | 1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Coronary Artery Disease, Coronary Disease, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Middle Aged, Phospholipases A2, Polymorphism, Single Nucleotide |
| Abstract | <p><b>AIMS: </b>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.</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSION: </b>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.</p> |
| DOI | 10.1093/eurheartj/ehr372 |
| Alternate Journal | Eur. Heart J. |
| PubMed ID | 22003152 |
| PubMed Central ID | PMC3258449 |
| Grant List | UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States R01 HL072810-06 / HL / NHLBI NIH HHS / United States HSN268200625226C / / PHS HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States R01 HL072810-07 / HL / NHLBI NIH HHS / United States R01 HL072810 / HL / NHLBI NIH HHS / United States HL64753 / HL / NHLBI NIH HHS / United States N01-HC-85079-86 / HC / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States AG028321 / AG / NIA NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States M01RR00425 / RR / NCRR NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States R01 HL098407 / HL / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States HL076784 / HL / NHLBI NIH HHS / United States R01 HL072810-09 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States R01 HL072810-08 / HL / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States |