Kim Jung Oh, Park Han Sung, Ko Eun Ju, Sung Jung Hoon, Kim Jinkwon, Oh Seung Hun, Kim Ok Joon, Kim Nam Keun
Theragen Bio Co., Ltd., Seongnam 13488, Korea.
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea.
J Pers Med. 2021 Mar 12;11(3):200. doi: 10.3390/jpm11030200.
Thymidylate synthase (TS) is a key gene involved in the repair of DNA damage and DNA synthesis that plays an important role in vascular development and recovery. In particular, TS gene polymorphisms play a major role in the progression of vascular disease and cancer metastasis. Therefore, the aim of this study was to investigate the association of three TS polymorphisms (1100T>C [rs699517], 1170A>G [rs2790], and 1494ins/del [rs151264360]) with ischemic stroke and silent brain infarction (SBI) in Koreans. A total of 1299 participants (507 stroke patients, 383 SBI patients, and 409 controls) were enrolled in the study. Genotyping of the three TS polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. To examine the association between TS gene polymorphisms and the diseases, we performed statistical analyses, including multivariable logistic regression and Fisher's exact tests. We found that TS 1100T>C and 1170A>G genotypes were strongly associated with ischemic stroke and SBI susceptibility. More specifically, the TS 1100T>C polymorphism was associated with the likelihood of ischemic stroke (TT vs. CC: AOR = 2.151, 95% CI = 1.275-3.628, = 0.004) and SBI (TT vs. TC+CC: AOR = 1.443, 95 % CI = 1.009-2.063, = 0.045). In contrast, the TS 1170A > G polymorphism exhibited lower correlation with the risk of stroke (AA vs. GG: AOR = 0.284, 95% CI = 0.151-0.537, < 0.0001) and SBI (AA vs. GG: AOR = 0.070, 95% CI = 0.016-0.298, = 0.0002). Furthermore, we confirmed that the TS 1100T>C polymorphism was synergistic with low folic acid levels (AOR = 6.749, < 0.0001). Altogether, these results suggest that TS 1100T>C and 1170A > G polymorphisms are associated with the risk of ischemic stroke and SBI, and our study provides the first evidence that 3'-UTR variants in TS are potential biomarkers in ischemic stroke and SBI.
胸苷酸合成酶（TS）是参与DNA损伤修复和DNA合成的关键基因，在血管发育和恢复中起重要作用。特别是，TS基因多态性在血管疾病进展和癌症转移中起主要作用。因此，本研究的目的是调查韩国人中TS的三种多态性（1100T>C [rs699517]、1170A>G [rs2790]和1494ins/del [rs151264360]）与缺血性中风和无症状脑梗死（SBI）之间的关联。共有1299名参与者（507名中风患者、383名SBI患者和409名对照）纳入本研究。通过聚合酶链反应-限制性片段长度多态性分析对TS的三种多态性进行基因分型。为了检验TS基因多态性与疾病之间的关联，我们进行了统计分析，包括多变量逻辑回归和Fisher精确检验。我们发现TS 1100T>C和1170A>G基因型与缺血性中风和SBI易感性密切相关。更具体地说，TS 1100T>C多态性与缺血性中风的可能性相关（TT与CC：比值比[AOR]=2.151，95%可信区间[CI]=1.275-3.628，P=0.004）和SBI（TT与TC+CC：AOR=1.443，95%CI=1.009-2.063，P=0.045）。相比之下，TS 1170A>G多态性与中风风险（AA与GG：AOR=0.284，95%CI=0.151-0.537，P<0.0001）和SBI（AA与GG：AOR=0.070，95%CI=0.016-0.298，P=0.0002）的相关性较低。此外，我们证实TS 1100T>C多态性与低叶酸水平具有协同作用（AOR=6.749，P<0.0001）。总之，这些结果表明TS 1100T>C和1170A>G多态性与缺血性中风和SBI风险相关，并且我们的研究提供了首个证据，表明TS中的3'-非翻译区变异体是缺血性中风和SBI的潜在生物标志物。
