Cardiovascular Research Institute (CVRI) Dublin, Mater Private Network, Dublin, Ireland; School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Cardiovascular Research Institute (CVRI) Dublin, Mater Private Network, Dublin, Ireland; School of Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Nitric Oxide. 2023 Sep 1;138-139:85-95. doi: 10.1016/j.niox.2023.07.001. Epub 2023 Jul 13.
Several published studies have reported an association between the Glu298Asp polymorphism (rs1799983), residing in the endothelial nitric oxide synthase (NOS3) gene, and lower levels of circulating nitric oxide, as well as an increased risk of coronary artery disease (CAD). However, association status of this genetic variant with acute coronary syndrome (ACS) or premature CAD (PCAD) is still unclear. Against this background, we conducted a systematic review and study level meta-analysis to assess the association of the NOS3 Glu298Asp polymorphism with ACS or PCAD.
A comprehensive online search to identify relevant studies was performed on several databases including PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science. The identified studies were stratified into two ancestral subgroups: 'European ancestry' and 'All other ancestries combined'. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random/fixed effects employing a Z test.
Out of a total of 195 distinct records identified through online search, 37 articles with 39 different studies, with a total sample size of 27,441 (11,516 cases/15,925 controls) were included for quantitative synthesis. Pooled results suggested significant associations of the NOS3 Glu298Asp polymorphism with ACS or PCAD through dominant as well as allelic genetic models (p ≤ 0.002), primarily driven by the 'All other ancestries combined' subgroup. The 'All other ancestries combined' subgroup demonstrated an additional risk of 36% for ACS or PCAD, through both dominant and allelic genetic models (OR = 1.36, 95%CI = 1.13, 1.63, p = 0.001 and OR = 1.36, 95%CI = 1.14, 1.61, p = 0.0005 respectively). On the other hand, the 'European ancestry' subgroup did not show any significant associations. Sensitivity analysis and a sub-analysis for the myocardial infarction endpoint further supported these observed associations.
This meta-analysis indicates towards an association between the NOS3 Glu298Asp polymorphism and ACS or PCAD, predominantly driven by 'All other ancestries combined' subgroup. In contrast, the 'European ancestry' subgroup did not demonstrate any significant association. Further large-scale investigations are required to confirm our derived results.
几项已发表的研究报告称，内皮型一氧化氮合酶（NOS3）基因中的 Glu298Asp 多态性（rs1799983）与循环一氧化氮水平降低以及冠心病（CAD）风险增加有关。然而，该遗传变异与急性冠状动脉综合征（ACS）或早发 CAD（PCAD）的关联状态尚不清楚。在此背景下，我们进行了系统评价和研究水平荟萃分析，以评估 NOS3 Glu298Asp 多态性与 ACS 或 PCAD 的相关性。
在包括 PubMed、EMBASE、MEDLINE、Scopus、Cochrane 图书馆和 Web of Science 在内的几个数据库中进行了全面的在线搜索，以确定相关研究。将确定的研究分为两个祖先亚组：“欧洲血统”和“所有其他血统合并”。使用 Z 检验通过随机/固定效应合并研究水平的比值比（OR）及其 95%置信区间（CI）。
通过在线搜索共确定了 195 个不同的记录，其中 37 篇文章包含 39 项不同的研究，总样本量为 27441 例（11516 例病例/15925 例对照），用于定量综合分析。合并结果表明，NOS3 Glu298Asp 多态性与 ACS 或 PCAD 之间存在显著关联，主要通过显性和等位基因遗传模型（p≤0.002），主要由“所有其他血统合并”亚组驱动。“所有其他血统合并”亚组通过显性和等位基因遗传模型显示 ACS 或 PCAD 的额外风险增加 36%（OR=1.36，95%CI=1.13，1.63，p=0.001 和 OR=1.36，95%CI=1.14，1.61，p=0.0005）。另一方面，“欧洲血统”亚组没有显示出任何显著的关联。敏感性分析和心肌梗死终点的亚分析进一步支持了这些观察到的关联。
这项荟萃分析表明，NOS3 Glu298Asp 多态性与 ACS 或 PCAD 之间存在关联，主要由“所有其他血统合并”亚组驱动。相比之下，“欧洲血统”亚组没有显示出任何显著的关联。需要进一步的大规模研究来证实我们的研究结果。
