Phospholipase A2 Receptor Gene Polymorphisms Alter its Functions and Present a Genetic Risk of an Increased Intima-Media Thickness of the Carotid Artery

Phospholipase A2 Receptor Gene 
Polymorphisms Alter its Functions and Present 
a Genetic Risk of an Increased Intima-Media 
Thickness of the Carotid Artery 
NGUYEN VAN SI. MD. PhD. 
University of Medicine and Pharmacy - Ho Chi Minh city 
Gia Dinh People’s Hospital 
Content 
• Introduction 
• Hypothesis 
• Method 
• Results 
• Discussion 
• Conclusion 
INTRODUCTION 
Inflammation and PLA2R 
Inflammation and PLA2R 
• Phospholipase A2 family 
– Highly related to inflammation via arachidonic 
acid pathway 
– Failure of PLA2 inhibitor in clinical trials 
(Darapladib) 
• Phospholipase A2 receptor 
– Specific receptor of PLA2 
– Important roles 
• Inflammatory reduction 
• Cell behaviors 
Inflammation and PLA2R 
• Hanasaki K et al. 2002. PLA2R: a regulator of 
biological functions of phospholipase A2 
• Mishina et al. 2014. Cardiac rupture after 
myocardial infarction 
– Lack of PLA2R: Less proliferation and migration 
SNPs of PLA2R gene 
• SNP: Single nucleotide polymorphism 
– Variation in a single nucleotide 
– May affect the function of the related protein 
• Two SNPs of PLA2R are completely linked 
Carotid Intima-media thickness (IMT) 
 • Related to atherosclerosis 
• Measured by echography 
• Important marker in high 
risk patients 
HYPOTHESIS 
Hypothesis 
• The effects of PLA2R polymorphisms in the 
development of IMT 
• PLA2R polymorphisms may alter cell behaviors 
METHOD 
Method 
• Clinical arm: Case-control study 
– 925 Japanese patients were genotyped for PLA2R 
SNPs at T/C rs3749117 and G/C rs35771982 
– 5 Mendelian inheritance models were used to 
check the relationship between PLA2R SNPs and 
increased IMT 
• Laboratory arm 
– HEK293 cell-line was transfected with PLA2R 
genes (wild type and double-mutated type) 
– Cell behaviors were compared 
RESULTS 
Baseline characteristics 
PLA2R-CC and increased IMT in males 
Case: 315 cases 
Control: 265 cases 
PLA2R-CC and increased IMT in males 
PLA2R SNPs in HEK293 cells 
A: Migration assay B: Proliferation assay 
DISCUSSION 
PLA2R-CC and increased IMT 
PLA2R SNPs 
-Reduce migration 
-Reduce proliferation 
Reduce endothelial 
repair 
PLA2R-CC and effects in male patients 
• Men have more risk factors of endothelial 
injury 
• Hormonal protection in women 
PLA2R-CC and effects in male patients 
CONCLUSION 
Conclusion 
• PLA2R SNPs at rs3749117 and rs35771982 are 
risk factors of increased IMT (CC genotype): 
OR = 1.93, p < 0.01 
• The relationship can be explained by the 
alteration in cell behaviors: reduced migration 
and proliferation 
Conclusion 
Endothelial layer Increased IMT 
Male patients 
More risk factors 
Injury 
PLA2R SNPs 
Reduced migration 
Reduced proliferation 
Less repair 
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