Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea.
Genetic Epidemiology Research Institute, Basgenbio Inc., Seoul 04167, Republic of Korea.
Int J Mol Sci. 2023 Aug 9;24(16):12591. doi: 10.3390/ijms241612591.
Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. While distinct features of CAD have been reported, the association between genetic factors and CAD in terms of biomarkers was insufficient. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase () gene, a gene involved in DNA synthesis and one-carbon metabolism. TS plays a critical role in maintaining the deoxythymidine monophosphate (dTMP) pool, which is essential for DNA replication and repair. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact gene expression and lead to dysfunction. Our findings strongly associate the 1100T>C and 1170A>G genotypes with CAD susceptibility. We observed that 1100T>C polymorphisms increased disease susceptibility in several groups, while the 1170A>G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the gene had the possibility of clinically useful biomarkers for the prevention, prognosis, and management of CAD in the Korean population.
冠状动脉疾病（CAD）是一种普遍存在的心血管疾病，其特征是冠状动脉内斑块的积累。虽然已经报道了 CAD 的不同特征，但在生物标志物方面，遗传因素与 CAD 之间的关联还不够充分。本研究旨在探讨遗传因素与 CAD 之间的联系，重点研究胸苷酸合成酶（TS）基因，该基因参与 DNA 合成和一碳代谢。TS 在维持脱氧胸苷单磷酸（dTMP）池方面起着关键作用，dTMP 池对于 DNA 复制和修复至关重要。因此，我们的研究针对可能影响基因表达并导致功能障碍的单核苷酸多态性。我们的研究结果强烈表明，1100T>C 和 1170A>G 基因型与 CAD 易感性相关。我们观察到，1100T>C 多态性增加了几个组的疾病易感性，而 1170A>G 多态性在与临床因素相互作用时显示出疾病风险降低的趋势。此外，我们的结果表明，1100/1170 单倍型可能对疾病易感性有贡献，表明其与临床因素在疾病发生中具有协同相互作用。基于这些发现，我们提出 TS 基因中的多态性有可能成为韩国人群 CAD 预防、预后和管理的临床有用生物标志物。
