Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Medicine (Baltimore). 2022 Jul 1;101(26):e29776. doi: 10.1097/MD.0000000000029776.
Recent experimental studies sparked the involvement of autophagy-related 7 (ATG7) in the development of atherosclerosis. However, the genetic variants and their association with coronary artery disease (CAD) are still to be unveiled. Therefore, we aimed to design a retrospective case-control study for the analysis of ATG7 gene polymorphisms and their association with CAD among the subjects originating from Pakistan. The ATG7 noncoding polymorphisms (rs1375206; Chr3:11297643 C/G and rs550744886; Chr3:11272004 C/G) were examined in 600 subjects, including 300 individuals diagnosed with CAD. Arginase-1 (ARG1) and nitric oxide metabolites were measured by the colorimetric enzymatic assay. Genotyping of noncoding ATG7 polymorphisms was accomplished by the polymerase chain reaction-restriction fragment length polymorphism method. A significant association of ATG7 (rs1375206 and rs550744886) was observed in individuals exhibiting CAD (P < .0001, for each single-nucleotide polymorphism). Moreover, variant allele G at both loci showed high occurrence and significant association with the disease phenotype as compared to the wild-type allele (odds ratio [OR] = 2.03, P < .0001 and OR = 2.08, P < .001, respectively). Variant genotypes at ATG7 rs1375206 and rs550744886 showed significant association with high concentrations of ARG1 and low nitric oxide metabolites among the patients (P < .0001 for each). A significant difference was noted in the distribution of the haplotype G-G, mapped at Chr3:11297643-11272004 between cases and controls (P < .0001). The study concludes that ATG7 polymorphisms are among the risk factors for CAD in the subjects from Pakistan. The study thus highlights the novel risk factors for high incidents of the disease and reported for the first time to the best of our knowledge.
最近的实验研究表明，自噬相关 7 （ATG7）参与了动脉粥样硬化的发生。然而，其遗传变异及其与冠心病（CAD）的关系仍有待揭示。因此，我们旨在设计一项回顾性病例对照研究，分析来自巴基斯坦的研究对象中 ATG7 基因多态性及其与 CAD 的关系。在 600 名研究对象中，包括 300 名被诊断为 CAD 的个体，检测了 ATG7 非编码多态性（rs1375206；Chr3:11297643 C/G 和 rs550744886；Chr3:11272004 C/G）。通过比色酶联测定法测量精氨酸酶-1（ARG1）和一氧化氮代谢物。非编码 ATG7 多态性的基因分型通过聚合酶链反应-限制性片段长度多态性方法完成。在患有 CAD 的个体中，ATG7（rs1375206 和 rs550744886）的多态性存在显著相关性（P<0.0001，每个单核苷酸多态性）。此外，与野生型等位基因相比，两个位点的变异等位基因 G 发生频率高且与疾病表型显著相关（比值比[OR]=2.03，P<0.0001 和 OR=2.08，P<0.001，分别）。ATG7 rs1375206 和 rs550744886 的变异基因型与患者中 ARG1 浓度升高和一氧化氮代谢物降低显著相关（每种情况 P<0.0001）。病例和对照组之间 Ch3:11297643-11272004 上的 G-G 单倍型分布存在显著差异（P<0.0001）。本研究得出结论，ATG7 多态性是巴基斯坦人群 CAD 的危险因素之一。因此，该研究强调了该疾病高发的新的危险因素，据我们所知，这是首次报道。
