1. NGUYEN VAN SI. MD. Supervisor: KYOTAKA KUGIYAMA. MD. PhD.
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.
Supervisor: KYOTAKA KUGIYAMA. MD. PhD.

2. Content
Introduction
Hypothesis
Method
Results
Discussion
Conclusion

3. INTRODUCTION

4. Cardiovascular disease

5. Inflammation and atherosclerosis

6. PLA2 and Inflammation

7. PLA2 and atherosclerosis

9. Inflammation and PLA2R Phospholipase A2 receptor Receptor of PLA2
Binding ability to collagen I
Important roles
Inflammatory reduction
Cell behaviors

10. Inflammation and PLA2R
Hanasaki K et al PLA2R: a regulator of biological functions of phospholipase A2
Mishina et al Cardiac rupture after myocardial infarction
Lack of PLA2R: Less proliferation and migration

11. 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

12. Carotid Intima-media thickness (IMT)
Related to atherosclerosis
Measured by echography
Important marker in high risk patients

13. HYPOTHESIS

14. Hypothesis
The effects of PLA2R polymorphisms in the development of IMT
PLA2R polymorphisms may alter cell behaviors

15. METHOD

16. Method Clinical arm: Case-control study
925 Japanese patients were genotyped for PLA2R SNPs at T/C rs and G/C rs
maxIMT measured by 2 cardiologists independently on Philips device
maxIMT cut-off: 1.1 mm
Logistic regression  relationship between genotypes and maxIMT

17. Method Clinical arm: Case-control study
5 Mendelian inheritance models (Logistic regression)
Dominant
Co-dominant
Recessive
Over-dominant
Log-additive

18. Method Laboratory arm PLA2R genes (wild type and mutated type)
HEK293 cell-line was transfected with PLA2R genes (wild type and double-mutated type)
Cell behaviors were compared
Migration
Proliferation

19. Method
Boyden chamber assay

20. Method
BrdU assay

21. RESULTS

22. Baseline characteristics

23. PLA2R-CC and increased IMT in males
Case: 315 cases
Control: 265 cases

24. PLA2R-CC and increased IMT in males

25. PLA2R SNPs in HEK293 cells
A: Migration assay
B: Proliferation assay

26. DISCUSSION

27. PLA2R-CC and increased IMT
PLA2R SNPs
Reduce migration
Reduce proliferation
Reduce endothelial repair

28. PLA2R-CC and effects in male patients
Men have more risk factors of endothelial injury
Hormonal protection in women

29. PLA2R-CC and effects in male patients

30. CONCLUSION

31. Conclusion
PLA2R SNPs at rs and rs 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

32. Reduced proliferation
Conclusion
Male patients
More risk factors
More injury
Endothelial layer
Increased IMT
PLA2R SNPs
Reduced migration
Reduced proliferation
Less repair

33. Thank you for listening