Holmes, Michael V and Exeter, Holly J and Folkersen, Lasse and Nelson, Christopher P and Guardiola, Montse and Cooper, Jackie A and Sofat, Reecha and Boekholdt, S Matthijs and Khaw, Kay-Tee and Li, Ka-Wah and Smith, Andrew JP and van’t Hooft, Ferdinand and Eriksson, Per and Franco-Cereceda, Anders and Asselbergs, Folkert W and Boer, Jolanda MA and Onland-Moret, N Charlotte and Hofker, Marten and Erdmann, Jeanette and Kivimaki, Mika and Kumari, Meena and Reiner, Alex P and Keating, Brendan J and Humphries, Steve E and Hingorani, Aroon D and Mallat, Ziad and Samani, Nilesh J and Talmud, Philippa J (2014) Novel Genetic Approach to Investigate the Role of Plasma Secretory Phospholipase A2 (sPLA <sub>2</sub> )-V Isoenzyme in Coronary Heart Disease. Circulation: Cardiovascular Genetics, 7 (2). pp. 144-150. DOI https://doi.org/10.1161/circgenetics.113.000271
Holmes, Michael V and Exeter, Holly J and Folkersen, Lasse and Nelson, Christopher P and Guardiola, Montse and Cooper, Jackie A and Sofat, Reecha and Boekholdt, S Matthijs and Khaw, Kay-Tee and Li, Ka-Wah and Smith, Andrew JP and van’t Hooft, Ferdinand and Eriksson, Per and Franco-Cereceda, Anders and Asselbergs, Folkert W and Boer, Jolanda MA and Onland-Moret, N Charlotte and Hofker, Marten and Erdmann, Jeanette and Kivimaki, Mika and Kumari, Meena and Reiner, Alex P and Keating, Brendan J and Humphries, Steve E and Hingorani, Aroon D and Mallat, Ziad and Samani, Nilesh J and Talmud, Philippa J (2014) Novel Genetic Approach to Investigate the Role of Plasma Secretory Phospholipase A2 (sPLA <sub>2</sub> )-V Isoenzyme in Coronary Heart Disease. Circulation: Cardiovascular Genetics, 7 (2). pp. 144-150. DOI https://doi.org/10.1161/circgenetics.113.000271
Holmes, Michael V and Exeter, Holly J and Folkersen, Lasse and Nelson, Christopher P and Guardiola, Montse and Cooper, Jackie A and Sofat, Reecha and Boekholdt, S Matthijs and Khaw, Kay-Tee and Li, Ka-Wah and Smith, Andrew JP and van’t Hooft, Ferdinand and Eriksson, Per and Franco-Cereceda, Anders and Asselbergs, Folkert W and Boer, Jolanda MA and Onland-Moret, N Charlotte and Hofker, Marten and Erdmann, Jeanette and Kivimaki, Mika and Kumari, Meena and Reiner, Alex P and Keating, Brendan J and Humphries, Steve E and Hingorani, Aroon D and Mallat, Ziad and Samani, Nilesh J and Talmud, Philippa J (2014) Novel Genetic Approach to Investigate the Role of Plasma Secretory Phospholipase A2 (sPLA <sub>2</sub> )-V Isoenzyme in Coronary Heart Disease. Circulation: Cardiovascular Genetics, 7 (2). pp. 144-150. DOI https://doi.org/10.1161/circgenetics.113.000271
Abstract
<jats:sec> <jats:title>Background—</jats:title> <jats:p> Secretory phospholipase A <jats:sub>2</jats:sub> (sPLA <jats:sub>2</jats:sub> ) enzymes are considered to play a role in atherosclerosis. sPLA <jats:sub>2</jats:sub> activity encompasses several sPLA <jats:sub>2</jats:sub> isoenzymes, including sPLA <jats:sub>2</jats:sub> -V. Although observational studies show a strong association between elevated sPLA <jats:sub>2</jats:sub> activity and CHD, no assay to measure sPLA <jats:sub>2</jats:sub> -V levels exists, and the only evidence linking the sPLA <jats:sub>2</jats:sub> -V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA <jats:sub>2</jats:sub> -V levels, we used <jats:italic>PLA2G5</jats:italic> mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA <jats:sub>2</jats:sub> -V in coronary heart disease (CHD) pathogenesis. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in <jats:italic>PLA2G5</jats:italic> showing the strongest association with <jats:italic>PLA2G5</jats:italic> mRNA expression levels as a proxy for sPLA <jats:sub>2</jats:sub> -V levels. We tested the association of this SNP with sPLA <jats:sub>2</jats:sub> 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 <jats:italic>PLA2G5</jats:italic> mRNA expression ( <jats:italic>P</jats:italic> =5.1×10 <jats:sup>−6</jats:sup> ). There was no association of rs525380C>A with plasma sPLA <jats:sub>2</jats:sub> activity (difference in geometric mean of sPLA <jats:sub>2</jats:sub> activity per rs525380 A-allele 0.4% (95% confidence intervals [−0.9%, 1.6%]; <jats:italic>P</jats:italic> =0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals [0.99, 1.04]; <jats:italic>P</jats:italic> =0.20). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p> 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 <jats:italic>PLA2G5</jats:italic> expression, a surrogate for sPLA <jats:sub>2</jats:sub> -V levels) and CHD events. The evidence does not support a causal role for sPLA <jats:sub>2</jats:sub> -V in CHD. </jats:p> </jats:sec>
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Mendelian randomization analysis |
| Subjects: | H Social Sciences > H Social Sciences (General) R Medicine > R Medicine (General) |
| Divisions: | Faculty of Social Sciences Faculty of Social Sciences > Institute for Social and Economic Research |
| SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
| Depositing User: | Unnamed user with email elements@essex.ac.uk |
| Date Deposited: | 29 Sep 2015 13:57 |
| Last Modified: | 04 Dec 2024 07:00 |
| URI: | http://repository.essex.ac.uk/id/eprint/15172 |