Medizinische Universität Graz - Research portal
Navigation/Search
- Researchers
- Institutions
- Projects
- Publications
- Partners
- Sponsors
- Equipment
- Knowhow
- Fields of Research
"Faces" of the day:
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Holmes, MV; Exeter, HJ; Folkersen, L; Nelson, CP; Guardiola, M; Cooper, JA; Sofat, R; Boekholdt, SM; Khaw, KT; Li, KW; Smith, AJ; Van't Hooft, F; Eriksson, P; Franco-Cereceda, A; Asselbergs, FW; Boer, JM; Onland-Moret, NC; Hofker, M; Erdmann, J; Kivimaki, M; Kumari, M; Reiner, AP; Keating, BJ; Humphries, SE; Hingorani, AD; Mallat, Z; Samani, NJ; Talmud, PJ; CARDIoGRAM Consortium.
Novel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels.
Circ Cardiovasc Genet. 2014; 7(2):144-150
Doi: 10.1161/CIRCGENETICS.113.000271
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Study Group Members Med Uni Graz:
- Stojakovic Tatjana
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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. 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). 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Alleles -
- Case-Control Studies -
- Coronary Disease - blood
- Coronary Disease - enzymology
- Coronary Disease - genetics
- Genotype -
- Group V Phospholipases A2 - blood
- Group V Phospholipases A2 - genetics
- Humans -
- Isoenzymes - blood
- Isoenzymes - genetics
- Mendelian Randomization Analysis -
- Polymorphism, Single Nucleotide -
- Find related publications in this database (Keywords)
- Mendelian randomization analysis