Jafarinejad-Farsangi Saeideh, Asgarian Sara, Ghahari Sara, Najd-Hassan-Bonab Leila, Moazzam-Jazi Maryam
Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cardiovasc Toxicol. 2025 Oct;25(10):1650-1672. doi: 10.1007/s12012-025-10050-2. Epub 2025 Aug 4.
The relevance of NOS3 common polymorphisms to coronary heart disease (CHD) risk is inconsistent among different studies, and little is known about the contribution of the genetic variants to the disease development across ancestries and age groups. To address this, we performed a comprehensive meta-analysis stratified by age and ancestry, including 123 eligible studies (29,040 cases and 26,694 controls). Random- or fixed-effects models were applied, based on heterogeneity statistics, to assess the association between the selected polymorphisms (rs1799983 and rs2070744) and CHD risk under various genetic models; p-values were corrected for multiple comparisons. Our findings indicate that the effect of both polymorphisms on the CHD risk varies across ancestries and age groups. In individuals under 55 years, rs1799983, but not rs2070744, showed a marginally significant association with CHD risk in the pooled analysis. However, neither variant appears to be involved in CHD development within any tested ancestry, including East Asian, European, Greater Middle Eastern, and South Asian populations. In individuals over 55 years, rs1799983 was significantly associated with an increased risk of CHD in East Asian, European, and Greater Middle Eastern populations, while rs2070744 contributed to CHD risk in East Asians and Europeans. Among all ancestries, both polymorphisms showed the strongest associations with the disease risk in East Asians, with no significant association observed in the American population. This meta-analysis advances our understanding of the impact of well-known NOS3 variants on CHD incidence across diverse age and ancestry groups. It proposes that the genetic risk of CHD associated with rs1799983 and rs2070744 might be more prominent in older individuals with prolonged environmental exposures. Such insights are critical for developing genetic screening panels to efficiently identify individuals who are genetically at high risk for CHD development.
一氧化氮合酶3（NOS3）常见多态性与冠心病（CHD）风险之间的相关性在不同研究中并不一致，而且对于这些基因变异在不同种族和年龄组疾病发展中的作用知之甚少。为了解决这个问题，我们进行了一项按年龄和种族分层的综合荟萃分析，纳入了123项符合条件的研究（29,040例病例和26,694例对照）。根据异质性统计结果，应用随机效应或固定效应模型，以评估所选多态性（rs1799983和rs2070744）与各种遗传模型下冠心病风险之间的关联；对p值进行多重比较校正。我们的研究结果表明，这两种多态性对冠心病风险的影响在不同种族和年龄组中有所不同。在55岁以下的个体中，rs1799983在汇总分析中与冠心病风险呈边缘显著关联，但rs2070744并非如此。然而，在任何测试的种族中，包括东亚、欧洲、中东和南亚人群，这两个变异似乎都不参与冠心病的发展。在55岁以上的个体中，rs1799983与东亚、欧洲和中东人群冠心病风险增加显著相关，而rs2070744则导致东亚人和欧洲人患冠心病的风险增加。在所有种族中，这两种多态性在东亚人与疾病风险的关联最强，在美国人群中未观察到显著关联。这项荟萃分析增进了我们对著名的NOS3变异对不同年龄和种族组冠心病发病率影响的理解。研究表明，与rs1799983和rs2070744相关的冠心病遗传风险在长期暴露于环境因素的老年个体中可能更为突出。这些见解对于开发基因筛查面板以有效识别冠心病发生遗传高危个体至关重要。
