Lp-PLA2 activity and PLA2G7 A379V genotype in patients with diabetes mellitus.
Lipoprotein associated phospholipase A2 (Lp-PLA2) modulates low-density lipoprotein (LDL) oxidation by hydrolysing oxidised phospholipids present on particle surfaces. We investigated whether Lp-PLA2 activity and PLA2G7 A379V genotype were related to mediators of atherosclerosis in a diabetic study. Plasma Lp-PLA2 activity (taken in men only) and A379V genotype were investigated with regards to metabolic syndrome (MS), UKPDS risk score, and oxidised LDL (oxLDL/LDL), in a cohort of Caucasian men and women (n=783, age 62.5+/-13.7 years). After adjustment for type of diabetes, CHD status, and statin use, those individuals with features defining the MS (WHO guidelines) had higher Lp-PLA2 activity (35.6+/-11.9 nmol/min/ml) compared to those without (33.0+/-10.8 nmol/min/ml) (p=0.02). Quartiles of UKPDS coronary heart disease (CHD) risk score were also positively associated with Lp-PLA2 activity (p=0.006, p=0.004 linear trend). Those men in the highest quartile of oxLDL/LDL level had the lowest Lp-PLA2 activity (31.3+/-10.5 nmol/min/ml) when compared to the middle two (32.3+/-9.8 and 35.9+/-10.9 nmol/min/ml, respectively) and lowest quartile (35.6 +/-12.5 nmol/min/ml; p=0.03, p=0.004 linear trend). There was no significant association between A379V genotype and Lp-PLA2 enzyme activity (p=0.34) or oxLDL/LDL (p=0.32). Lp-PLA2 activity is an independent predictor of CHD risk and MS in a sample of subjects with diabetes mellitus. The association of Lp-PLA2 activity with oxLDL/LDL suggests that Lp-PLA2 may be a modulating factor in the process of atherosclerosis.
Wootton
P T E
PT
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, Rayne Building, 5 University Street, London WC1E 6JF, UK.
Stephens
J W
JW
Hurel
S J
SJ
Durand
H
H
Cooper
J
J
Ninio
E
E
Humphries
S E
SE
Talmud
P J
PJ
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000209:etiology; D004247:DNA / Q000235:genetics*; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010741:Phospholipases A / Q000097:blood / Q000235:genetics*; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012307:Risk Factors
D008078:Cholesterol, LDL; D004247:DNA; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase