内皮型一氧化氮合酶、基质金属蛋白酶 3、血管紧张素原和血管紧张素 II 型 1 型受体多态性与经皮冠状动脉介入治疗后再狭窄风险的关联：一项荟萃分析。
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.
机构信息
Department of Pharmacy, Peking University First Hospital, Beijing, People's Republic of China; Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
Department of Pharmacy, Peking University First Hospital, Beijing, People's Republic of China.
出版信息
Clin Ther. 2020 Mar;42(3):458-474. doi: 10.1016/j.clinthera.2020.01.018. Epub 2020 Feb 21.
PURPOSE
Previous 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.
METHODS
We 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.
FINDINGS
A 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).
IMPLICATIONS
The 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.
目的
先前的研究报告称，经皮冠状动脉介入治疗（PCI）后，内皮型一氧化氮合酶（eNOS）、基质金属蛋白酶 3（MMP-3）、血管紧张素原（AGT）和血管紧张素 II 型 1 型受体（AT1R）的多态性与再狭窄的风险相关，结果存在争议。本研究旨在总结这些多态性与 PCI 后再狭窄风险之间的关系。
方法
我们在 PubMed、Embase、Cochrane 图书馆和 ClinicalTrials.gov 电子数据库中检索了与 eNOS、MMP-3、AGT 和 AT1R 多态性与再狭窄相关的研究。
结果
共分析了 17 项研究（7781 例患者），包括 5 项关于 eNOS G298A（n=912）的研究、5 项关于 MMP3 5A/6A（n=4519）的研究、6 项关于 AGT M235T（n=1801）的研究和 7 项关于 AT1R A1166C（n=2477）的研究。对于 eNOS 基因的 G298A 变体，等位基因优势比（OR）为 1.685（95%CI，1.269-2.338；P<0.001），杂合子 OR 为 2.144（95%CI，1.490-3.085；P<0.001），显性 OR 为 2.078（95%CI，1.462-2.954；P<0.001），超显性 OR 为 0.496（95%CI，0.348-0.706；P<0.001）。对于 MMP3 基因的 5A/6A 变体，杂合子 OR 为 0.839（95%CI，0.722-0.975；P=0.022），显性 OR 为 0.846（95%CI，0.733-0.976；P=0.022），超显性 OR 为 1.141（95%CI，1.001-1.301；P=0.049）。对于 AGT 基因的 M235T 变体，杂合子 OR 为 1.594（95%CI，1.179-2.155；P=0.002），显性 OR 为 1.437（95%CI，1.077-1.918；P=0.014），超显性 OR 为 0.694（95%CI，0.555-0.869；P=0.001）。在 AT1R 基因 A1166C 多态性下，3 种模型（纯合子 OR=2.009；95%CI，1.433-2.816；P<0.001；隐性 OR 1.874；95%CI，1.353-2.595；P<0.001；显性 OR=1.350；95%CI，1.105-1.649；P=0.003）均显示阳性结果。
结论
eNOS 的 G298A 变体、MMP3 的 5A/6A 变体、AGT 的 M235T 变体和 AT1R 的 A1166C 变体可能会增加 PCI 后再狭窄的风险。
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