Effects of V279F in the Lp-PLA(2) gene on markers of oxidative stress and inflammation in Koreans.
BACKGROUND
A single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) gene is known to influence enzyme activity. It is unclear whether Lp-PLA(2) exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA(2) activity, oxidative stress and inflammation.


METHODS
We genotyped 2914 healthy Koreans (43-79years) for the Lp-PLA(2) V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA(2) levels.


RESULTS
Lp-PLA(2) activity was 24% lower in V/F subjects (n=641) than in those with the V/V genotype (n=2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA(2) activity was positively correlated with LDL-cholesterol (r=0.134, P<0.001), ox-LDL (r=0.064, P<0.01), 8-epi-PGF(2alpha) (r=0.198, P<0.001), free fatty acid (r=0.082, P<0.001), and fibrinogen (r=0.112, P<0.01) levels. Additionally, ox-LDL, 8-epi-PGF(2alpha), free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9+/-0.69, V/F: 119.4+/-1.26, F/F: 109.2+/-4.84mg/dl, P=0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (> or =130mg/dl) (P=0.003) but not in those with low LDL-cholesterol (<130mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25+/-0.09, V/F: 0.97+/-0.12, F/F: 3.20+/-0.88mg/dl, P<0.001).


CONCLUSIONS
The recessive effects of Lp-PLA(2) V279F on LDL-cholesterol and significant correlations between Lp-PLA(2) activity and LDL-cholesterol, 8-epi-PGF(2alpha) and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA(2) activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation.
Paik
Jean Kyung
JK
Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea.
Chae
Jey Sook
JS
Jang
Yangsoo
Y
Kim
Ji Young
JY
Kim
Oh Yoen
OY
Jeong
Tae-Sook
TS
Lee
Sang-Hyun
SH
Lee
Jong Ho
JH
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D000328:Adult; D000368:Aged; D015415:Biomarkers; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007723:Korea; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D015415:Biomarkers; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase