Systematic Review and Meta-Analysis of SERPINE1 4G/5G Insertion/Deletion Variant With Circulating Lipid Levels

BACKGROUND: Recent studies have shown that the 4G/5G insertion/deletion variant of SERPINE1 (rs1799889) is closely linked to coronary artery disease (CAD). This study aims to clarify the effects of the rs1799889 variant on lipid levels and to insight into the mechanisms underlying the rs1799889 variant and CAD. METHODS AND RESULTS: By searching PubMed and the Cochrane databases for studies published before 31 October 2021, 40 studies conducted on a total of 13,117 subjects were included for the analysis. The consistent findings for the effects of the 5G allele of rs1799889 variant on lipid metabolism were the significantly decreased triglycerides (TG) [standardized mean difference (SMD) = –0.12, 95% CI = –0.21 to 0.03, P = 0.01], total cholesterol (TC) (SMD = –0.12, 95% CI = –0.17 to 0.06, P < 0.001), and low-density lipoprotein cholesterol (LDL-C) (SMD = –0.13, 95% CI = –0.23 to 0.03, P = 0.01) levels. Intriguingly, the significant effects of the rs1799889 variant on LDL-C (SMD = –0.15, 95% CI = –0.26 to 0.05, P < 0.01) and TC (SMD = –0.17, 95% CI = –0.27 to 0.07, P < 0.01) levels were primarily observed in the Asian population. However, the significant effect of the rs1799889 variant on high-density lipoprotein cholesterol (HDL-C) (SMD = 0.26, 95% CI = 0.03–0.48, P = 0.03) levels was detected only in female subjects. CONCLUSION: The rs1799889 variant of SERPINE1 is a protective genetic factor against CAD, the Asian population with the 5G allele of the rs1799889 variant may have a reduced CAD risk.