The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men.
OBJECTIVE
It is unclear whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA(2) variant (V279F and A379V) and CVD in Korean men.


METHODS
CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA(2) polymorphism (V279F and A379V).


METHODS
We calculated odds ratio (OR) on CVD risk and measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle size, oxidized LDL, lipid peroxides, and Lp-PLA(2) activity.


RESULTS
The presence of the 279F allele was associated with a lower risk of CVD [OR 0.646 (95% confidence interval 0.490-0.850), P = 0.002], and the association still remained after adjustments for age, body mass index, waist circumference, waist to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95% confidence interval 0.512-0.911), P = 0.009]. Lp-PLA(2) activity was lower in CVD patients taking a lipid-lowering drug (31%), those not taking a lipid-lowering drug (26%), and control subjects (23%) with the V/F genotype, compared with those with the V/V genotype. Subjects with the F/F genotype in controls and two CVD patients groups showed no appreciable enzymatic activity. Control subjects with the V/F genotype had larger LDL particle size than those with the V/V genotype. In addition, control subjects carrying the F allele showed lower malondialdehyde concentrations. On the other hand, we found no significant relationship between A379V genotype and CVD risk.


CONCLUSIONS
The association of the F279 loss of function variant with the reduced risk of CVD supports the concept that Lp-PLA(2) plays a proatherogenic and causative role in CVD.
Jang
Yangsoo
Y
Department of Food and Nutrition, Yonsei University, 134 Shinchon-Ding, Sudaemun-Gu, Seoul 120-749, Korea.
Kim
Oh Yoen
OY
Koh
Soo Jeong
SJ
Chae
Jey Sook
JS
Ko
Young Guk
YG
Kim
Ji Young
JY
Cho
Hongkeun
H
Jeong
Tae-Sook
TS
Lee
Woo Song
WS
Ordovas
Jose M
JM
Lee
Jong Ho
JH
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D004247:DNA / Q000235:genetics; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005838:Genotype; D006801:Humans; D007723:Korea; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D010316:Particle Size; D010741:Phospholipases A / Q000235:genetics* / Q000378:metabolism; D054467:Phospholipases A2; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
D008077:Lipoproteins, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein; C075750:8-epi-prostaglandin F2alpha; D008315:Malondialdehyde; D004247:DNA; D002784:Cholesterol; D015237:Dinoprost; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase