Research Repository

Novel genetic approach to investigate the role of plasma secretory phospholipase a2 (spla2)-v isoenzyme in coronary heart disease

Holmes, MV and Exeter, HJ and Folkersen, L and Nelson, CP and Guardiola, M and Cooper, JA and Sofat, R and Boekholdt, SM and Khaw, KT and Li, KW and Smith, AJP and Van't Hooft, F and Eriksson, P and Franco-Cereceda, A and Asselbergs, FW and Boer, JMA and Onland-Moret, NC and Hofker, M and Erdmann, J and Kivimaki, M and Kumari, M and Reiner, AP and Keating, BJ and Humphries, SE and Hingorani, AD and Mallat, Z and Samani, NJ and Talmud, PJ (2014) 'Novel genetic approach to investigate the role of plasma secretory phospholipase a2 (spla2)-v isoenzyme in coronary heart disease.' Circulation: Cardiovascular Genetics, 7 (2). 144 - 150. ISSN 1942-325X

Full text not available from this repository.

Abstract

Background-Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis. Methods and Results-Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5 mRNA expression levels as a proxy for sPLA2-V levels. We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case- control studies with 27 230 events and 70 500 controls. rs525380C>A showed the strongest association with PLA2G5 mRNA expression (P=5.1×10-6). There was no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals [-0.9%, 1.6%]; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals [0.99, 1.04]; P=0.20). Conclusions-This novel approach for single-nucleotide polymorphism selection for this modified Mendelian randomization analysis showed no association between rs525380 (the lead single-nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels) and CHD events. The evidence does not support a causal role for sPLA2-V in CHD. © 2014 American Heart Association, Inc.

Item Type: Article
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Clare Chatfield
Date Deposited: 29 Sep 2015 13:57
Last Modified: 04 Feb 2019 11:16
URI: http://repository.essex.ac.uk/id/eprint/15172

Actions (login required)

View Item View Item