Tính đa hình gen thụ thể phosholipase a2 tác động lên chức năng và nguy cơ dày nội mạc động mạch cảnh

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.. Cardiac rupture

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

INTRODUCTION

Inflammation and PLA2R

Inflammation and PLA2R

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

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

Less repair

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