Lp-PLA2 activity and PLA2G7 A379V genotype in patients with diabetes mellitus

Abstract

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.