Platelet-activating factor-acetylhydrolase A379V (exon 11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction.
BACKGROUND
Oxidation of low density lipoproteins is an initial step of atherogenesis that generates pro-inflammatory phospholipids, including platelet-activating factor (PAF). PAF is degraded by PAF-acetylhydrolase (PAF-AH), which has been postulated to be a risk factor for myocardial infarction (MI). The role of PAF-AH for the onset of premature MI is unclear.


METHODS
Polymorphisms located in putatively functional regions were investigated in a cohort of patients having premature MI onset prior to 46 years of age (n = 200) and a sex-age-matched control group (n = 200). The activity of PAF-AH and coronary angiograms were evaluated for the severity of coronary atherosclerosis.


RESULTS
The V allele of A379V (exon 11) polymorphism on PAF-AH gene was more frequent in patients with premature MI (P = 0.001). This V allele polymorphism was also associated with a lower activity of plasma PAF-AH and a more complex coronary atherosclerosis (p Trends <0.05). Multiple logistic regression analysis showed that this polymorphism was an independent risk factor (Odds Ratio [OR] 1.66, 95% CI 1.14.1 to 5.80, P = 0.008) as well as smoking (OR 3.72, 95% CI 1.77 to 9.28, P = 0.001), diabetes mellitus (OR 2.25, 95% CI 1.40 to 5.32, P = 0.007) and hypertension (OR 1.88, 95% CI 1.25 to 5.36, P = 0.003) for the onset of premature MI.


CONCLUSIONS
We conclude that a functional and significant association between the A379V polymorphism on exon 11 of PAF-AH gene and premature MI exists in this Taiwanese population. This polymorphism is significantly associated with the PAF-AH activity and the severity of coronary atherosclerosis.
Liu
P-Y
PY
Division of Cardiology, Departments of Internal Medicine, National Cheng-Kung University Medical Center, 138 Sheng-Li Road, Tainan 704, Taiwan.
Li
Y-H
YH
Wu
H-L
HL
Chao
T-H
TH
Tsai
L-M
LM
Lin
L-J
LJ
Shi
G-Y
GY
Chen
J-H
JH
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D015331:Cohort Studies; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics*; D010741:Phospholipases A / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors
D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase