Secretory phospholipase A(2)-IIA and cardiovascular disease: a mendelian randomization study
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BiBTeXOBJECTIVES\backslashr\backslashnThis study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.\backslashr\backslashnBACKGROUND\backslashr\backslashnHigher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy.\backslashr\backslashnMETHODS\backslashr\backslashnWe conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable.\backslashr\backslashnRESULTS\backslashr\backslashnPLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnReducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
DOI: 10.1016/j.jacc.2013.06.044
Projects: Genetical Statistics and Systems Biology
Publication type: Journal article
Journal: Journal of the American College of Cardiology
Human Diseases: No Human Disease specified
Citation: Journal of the American College of Cardiology 62(21):1966-1976
Date Published: 1st Nov 2013
Registered Mode: imported from a bibtex file
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The group is interested in omic-level studies including the genome, methylome, transcriptome, and metabolome of the general population as well as of various diseases including cardiovascular diseases, pneumonia, sepsis, obesity, and brain cancers. Additionally, we aim at transfering results of biomathematical model simulations into clinical practice e.g. by haematopoietic growth-factor opimization during cytotoxic chemotherapy and optimization of EPO applications in chronic kidney disease.
The ...
Programme: This Project is not associated with a Programme
Public web page: http://www.imise.uni-leipzig.de/en/Groups/GenStat/
Start date: 1st Jan 2013
https://orcid.org/0000-0002-8683-7084
Projects: LIFE Heart, LIFE - Leipzig Research Center for Civilization Diseases, HaematoOpt - Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, e:Med, Genetical Statistics and Systems Biology, Task Force COVID-19 Leipzig, NFDI4Health
Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)
Markus Scholz Scientific Speaker Institution Institut für Medizinische Informatik, Statistik und Epidemiologie Universität Leipzig Härtelstraße 16-18 04107 Leipzig
