Tính đa hình gen thụ thể phosholipase a2 tác động lên chức năng và nguy cơ dày nội mạc động mạch cảnh
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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
NGUYEN VAN SI. MD. PhD.
University of Medicine and Pharmacy - Ho Chi Minh city
Gia Dinh People’s Hospital
Content
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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
Male patients
More risk factors
Injury
Endothelial layer
Increased IMT
Less repair
PLA2R SNPs
Reduced migration
Reduced proliferation
