Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Casas, JP; Ninio, E; Panayiotou, A; Palmen, J; Cooper, JA; Ricketts, SL; Sofat, R; Nicolaides, AN; Corsetti, JP; Fowkes, FG; Tzoulaki, I; Kumari, M; Brunner, EJ; Kivimaki, M; Marmot, MG; Hoffmann, MM; Winkler, K; März, W; Ye, S; Stirnadel, HA; Boekholdt, SM; Khaw, KT; Humphries, SE; Sandhu, MS; Hingorani, AD; Talmud, PJ.
PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry.
Circulation. 2010; 121(21):2284-2293
Doi: 10.1161/CIRCULATIONAHA.109.923383
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- März Winfried
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Higher lipoprotein-associated phospholipase A(2)(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17). Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD.
- Find related publications in this database (using NLM MeSH Indexing)
- 1-Alkyl-2-acetylglycerophosphocholine Esterase - metabolism
- Case-Control Studies -
- Coronary Disease - enzymology
- Coronary Disease - epidemiology
- Coronary Disease - genetics
- Cross-Sectional Studies -
- Cross-Sectional Studies -
- Genotype -
- Humans -
- Phospholipases A2 - genetics
- Polymorphism, Single Nucleotide - genetics
- Prospective Studies -
- Risk Factors -
- Find related publications in this database (Keywords)
- epidemiology
- genetics
- mendelian randomization analysis
- risk factors