Objectives Lipoprotein-Associated Phospholipase A2 (Lp-PLA2), an enzyme produced by inflammatory cells, is an emerging risk factor and a potential therapeutic target. Findings from previous studies investigating the association between PLA2G7 gene (encode Lp-PLA2 protein) polymorphisms and Lp-PLA2 activity are inconsistent. Hence, a meta-analysis with multiethnic populations was conducted to evaluate the association between four well-characterised PLA2G7 gene polymorphisms (A379V, V279F, I198T and R92H) and Lp-PLA2 activity.
Methods MEDLINE, EMBASE, CNKI (Chinese National Knowledge Infrastructure) and Wanfang databases (prior to January 2013) were searched for case-control, nested case-control, or cross-sectional studies on the association between PLA2G7 polymorphisms and Lp-PLA2 activity. Duplicate publications, studies without interested loci, or Genome-Wide Association (GWA) studies were excluded. Data from an unpublished study with a total of 1268 subjects were included as well. Standardised mean difference (SMD) and its corresponding 95% confidence interval (CI) were calculated to assess the association between PLA2G7 polymorphisms and Lp-PLA2 activity. A panel of subgroup analyses was also conducted.
Results A total of 11 articles involving 4 polymorphisms in PLA2G7 gene were included (A379V (6 articles), V279F (6 articles), I198T (5 articles) and R92H (5 articles)). A379V was significantly associated with an elevated Lp-PLA2 activity, yielding a pooled SMD of 0.15 (0.06, 0.24) for comparison of AV vs. AA, 0.30(0.18, 0.42) for comparison of VV vs. AA, 0.06(0.01, 0.12) under dominant model and 0.19(0.08, 0.30) under recessive model. Subgroup analysis showed a significant ethnic difference, with the impact of A379V was only found in Caucasians. V279F was only found in Asians and significantly associated with a decreased Lp-PLA2 activity, yielding SMD of -1.54(-1.84,-1.24) for comparison of VF vs. VV, -2.92(-3.37,-2.48) for comparison of FF vs. VV, -1.52(-1.57, -1.46) under dominant model and -2.96(-3.10, -2.82) under recessive model. R92H was associated with Lp-PLA2 activity for comparison of RH vs. RR (SMD = -0.11, 95%CI: -0.16 to -0.05, P < 0.001) and dominant model (SMD = -0.11, 95%CI: -0.16 to -0.06, P < 0.001), with the significant impact only found in Caucasians by subgroup analysis. The overall impact of I198T polymorphism was not significantly associated with Lp-PLA2 activity. However, in Asians, I198T was found to be associated with Lp-PLA2 activity for comparison of IT vs. II (SMD = -0.53, 95%CI: -0.68 to -0.37, P < 0.001) and dominant model (SMD = -0.53, 95%CI: -0.68 to -0.38, P < 0.001).
Conclusions This meta-analysis found that A379V, V279F, and R92H were associated with Lp-PLA2 activity, with a remarkable ethnic difference existing. Our findings may provide important information for the identification of high-risk individuals of cardiovascular disease and target population for the potential intervention with Lp-PLA2 inhibitor.