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The 3′-UTR Polymorphisms in the Thymidylate Synthase (TS) Gene Associated with the Risk of Ischemic Stroke and Silent Brain Infarction

1
Theragen Bio Co., Ltd., Seongnam 13488, Korea
2
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea
3
CHA Bundang Medical Center, Department of Neurology, School of Medicine, CHA University, Seongnam 13496, Korea
*
Authors to whom correspondence should be addressed.
Academic Editors: Mayra Paolillo and Chiara Villa
J. Pers. Med. 2021, 11(3), 200; https://doi.org/10.3390/jpm11030200
Received: 16 January 2021 / Revised: 5 March 2021 / Accepted: 9 March 2021 / Published: 12 March 2021
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, P = 0.004) and SBI (TT vs. TC+CC: AOR = 1.443, 95 % CI = 1.009–2.063, P = 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, P < 0.0001) and SBI (AA vs. GG: AOR = 0.070, 95% CI = 0.016–0.298, P = 0.0002). Furthermore, we confirmed that the TS 1100T>C polymorphism was synergistic with low folic acid levels (AOR = 6.749, P < 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. View Full-Text
Keywords: thymidylate synthase; ischemic stroke mortality; single nucleotide polymorphism thymidylate synthase; ischemic stroke mortality; single nucleotide polymorphism
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MDPI and ACS Style

Kim, J.O.; Park, H.S.; Ko, E.J.; Sung, J.H.; Kim, J.; Oh, S.H.; Kim, O.J.; Kim, N.K. The 3′-UTR Polymorphisms in the Thymidylate Synthase (TS) Gene Associated with the Risk of Ischemic Stroke and Silent Brain Infarction. J. Pers. Med. 2021, 11, 200. https://doi.org/10.3390/jpm11030200

AMA Style

Kim JO, Park HS, Ko EJ, Sung JH, Kim J, Oh SH, Kim OJ, Kim NK. The 3′-UTR Polymorphisms in the Thymidylate Synthase (TS) Gene Associated with the Risk of Ischemic Stroke and Silent Brain Infarction. Journal of Personalized Medicine. 2021; 11(3):200. https://doi.org/10.3390/jpm11030200

Chicago/Turabian Style

Kim, Jung O., Han S. Park, Eun J. Ko, Jung H. Sung, Jinkwon Kim, Seung H. Oh, Ok J. Kim, and Nam K. Kim. 2021. "The 3′-UTR Polymorphisms in the Thymidylate Synthase (TS) Gene Associated with the Risk of Ischemic Stroke and Silent Brain Infarction" Journal of Personalized Medicine 11, no. 3: 200. https://doi.org/10.3390/jpm11030200

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