Associations Between Polymorphisms of Endothelial Nitric Oxide Synthase, Matrix Metalloproteinase 3, Angiotensinogen, and Angiotensin II Type 1 Receptor and Risk of Restenosis After Percutaneous Coronary Intervention: A Meta-analysis

Abstract

PurposePrevious studies have reported controversial results regarding the risk of restenosis with polymorphisms of endothelial nitric oxide synthase (eNOS), matrix metalloproteinase 3 (MMP-3), angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1R) after percutaneous coronary intervention (PCI). This study aimed to summarize the association between these polymorphisms and risk of restenosis after PCI. MethodsWe searched the electronic databases of PubMed, Embase, Cochrane's Library, and ClinicalTrials.gov for studies on the association of eNOS, MMP-3, AGT, and AT1R polymorphisms with restenosis. FindingsA total of 17 studies (7781 patients) were analyzed, including 5 studies on eNOS G298A (n = 912), 5 studies on MMP3 5A/6A (n = 4519), 6 studies on AGT M235T (n = 1801), and 7 studies on AT1R A1166C (n = 2477). For the G298A variant of the eNOS gene, the allele odds ratio (OR) was 1.685 (95% CI, 1.269–2.338; P < 0.001), the heterozygote OR was 2.144 (95% CI, 1.490–3.085; P < 0.001), the dominant OR was 2.078 (95% CI, 1.462–2.954; P < 0.001), and the overdominant OR was 0.496 (95% CI, 0.348–0.706; P < 0.001). For the 5A/6A variant of the MMP3 gene, the heterozygote OR was 0.839 (95% CI, 0.722–0.975; P = 0.022), the dominant OR was 0.846 (95% CI, 0.733–0.976; P = 0.022), and the overdominant OR was 1.141 (95% CI, 1.001–1.301; P = 0.049). For the M235T variant of the AGT gene, the heterozygote OR was 1.594 (95% CI, 1.179–2.155; P = 0.002), the dominant OR was 1.437 (95% CI, 1.077–1.918; P = 0.014), and the overdominant OR was 0.694 (95% CI, 0.555–0.869; P = 0.001). Positive results were observed in the AT1R gene A1166C polymorphism under 3 models (homozygote OR = 2.009; 95% CI, 1.433–2.816; P < 0.001; recessive OR 1.874; 95% CI, 1.353–2.595; P < 0.001; and dominant OR = 1.350; 95% CI, 1.105–1.649; P = 0.003). ImplicationsThe G298A variant of eNOS, the 5A/6A variant of MMP3, the M235T variant of AGT, and the A1166C variant of A1TR may increase the risk of restenosis after PCI.