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Phospholipase A2 Receptor Gene Polymorphisms Alter its Functions and Present a Genetic Risk of an Increased Intima-Media Thickness of the Carotid Artery
- Source :
- Journal of Atherosclerosis and Thrombosis
- Publication Year :
- 2016
- Publisher :
- Japan Atherosclerosis Society, 2016.
-
Abstract
- Aims: Phospholipase A2 receptor 1 (PLA2R) has multiple biological functions other than functioning as a receptor for secretory PLA2s. Two nonsynonymous polymorphisms in the C-type lectin-like domains (CTLD) 1 of PLA2R gene have been associated with idiopathic membranous nephropathy. This study examined whether the same PLA2R polymorphisms may alter functions of PLA2R in cells expressing the variant PLA2R. In addition, the clinical relevance of the experiment was examined. Methods: Two nonsynonymous polymorphisms (T/C at rs3749117 and G/C at rs35771982) in CTLD1 of PLA2R gene were completely linked. HEK293 cells expressing human wild-type PLA2R (T at rs3749117 and G at rs35771982) or human mutant PLA2R that had double mutations (C at rs3749117 and C at rs35771982) were constructed. Results: HEK293 cells expressing mutant PLA2R had lower migratory and proliferative responses to collagen I compared with cells expressing wild-type PLA2R. In 580 male patients, PLA2R gene polymorphisms were associated with an increase in maximum intima-media thickness (maxIMT) of the carotid artery. The multivariate regression model showed that PLA2R gene polymorphisms were a risk factor of an increased maxIMT that was independent of conventional risk factors (OR = 1.93, 95% CI: 1.17–3.19, p < 0.01). Conclusions: The nonsynonymous common variants of PLA2R gene altered biological functions in cells expressing variant PLA2R. PLA2R gene polymorphisms present a genetic risk of an increased IMT of the carotid artery in male. The functional changes in the variant PLA2R may potentially be responsible for its association with an increased IMT of the carotid artery.
- Subjects :
- Male
Chest Pain
Blotting, Western
Phospholipase A2 receptor
Apoptosis
Real-Time Polymerase Chain Reaction
Carotid Intima-Media Thickness
Polymorphism, Single Nucleotide
Risk Assessment
Cell Movement
Human Umbilical Vein Endothelial Cells
Humans
RNA, Messenger
Cells, Cultured
Aged
Cell Proliferation
Reverse Transcriptase Polymerase Chain Reaction
Receptors, Phospholipase A2
Gene polymorphism
Middle Aged
Atherosclerosis
Flow Cytometry
HEK293 Cells
Original Article
Female
Carotid artery
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 18803873 and 13403478
- Volume :
- 23
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of Atherosclerosis and Thrombosis
- Accession number :
- edsair.pmid..........b6e169f4a5e9887e62cf15e1e8482b9f