Department of Community Health and Epidemiology, Queen's University, Kingston, Ontario, Canada.
Mol Genet Metab. 2010 Sep;101(1):18-24. doi: 10.1016/j.ymgme.2010.05.010. Epub 2010 Jun 9.
Thymidylate synthase (TS) is a key enzyme that regulates the production of nucleotide synthesis by catalyzing the conversion of deoxyuridylate to thymidylate. Three functional polymorphisms in the TS gene have been identified including: (i) the thymidylate synthase enhancer region (TSER) tandem repeat polymorphism and (ii) the G to C single nucleotide polymorphism (G/C SNP) both of which occur in the 5'untranslated region (UTR) of the TS gene; and (iii) the 6 base pair deletion at base pair 1494 (TS1494del6) located in the 3'UTR.
The purpose of this research was to investigate the relationship between TS polymorphisms and total plasma homocysteine (tHcy) levels.
The study population consisted of 396 healthy male and female volunteers from Kingston, Ontario and Halifax, Nova Scotia, Canada between 2006 and 2008. The effect of each TS polymorphism on tHcy concentrations was investigated and further analyses were conducted on categorization of polymorphisms based on 5' or 3'UTR. The combined effect of TS polymorphisms on tHcy concentration was also investigated, in addition to interactions between polymorphisms in TS and MTHFR 677C>T and interactions between TS polymorphisms and serum folate and vitamin B(12) status.
An association between TS 5'polymorphisms and tHcy concentration was observed (p=0.05). The combined effect of the TS polymorphisms was also found to be associated with tHcy concentration (p=0.05). Additionally, an antagonistic interaction was observed between TS 5'polymorphism and MTHFR 677C>T on tHcy concentrations (p=0.04).
The findings of this research provide evidence of an association between TS polymorphisms and tHcy concentrations.
胸苷酸合成酶（TS）是一种关键的酶，通过催化脱氧尿苷酸转化为胸苷酸来调节核苷酸的合成。在 TS 基因中已经鉴定出三个功能多态性，包括：（i）胸苷酸合成酶增强子区域（TSER）串联重复多态性和（ii）发生在 TS 基因 5'非翻译区（UTR）中的 G 到 C 单核苷酸多态性（G/C SNP）；以及（iii）位于 3'UTR 中的第 1494 位碱基对的 6 个碱基缺失（TS1494del6）。
本研究旨在探讨 TS 多态性与总血浆同型半胱氨酸（tHcy）水平之间的关系。
本研究人群包括 2006 年至 2008 年期间来自安大略省金斯敦和新斯科舍省哈利法克斯的 396 名健康男性和女性志愿者。研究了每个 TS 多态性对 tHcy 浓度的影响，并进一步基于 5'或 3'UTR 对多态性进行了分类分析。还研究了 TS 多态性对 tHcy 浓度的综合影响，以及 TS 和 MTHFR 677C>T 多态性之间的相互作用以及 TS 多态性与血清叶酸和维生素 B(12)状态之间的相互作用。
观察到 TS 5'多态性与 tHcy 浓度之间存在关联（p=0.05）。还发现 TS 多态性的综合效应与 tHcy 浓度相关（p=0.05）。此外，还观察到 TS 5'多态性与 MTHFR 677C>T 之间在 tHcy 浓度上存在拮抗相互作用（p=0.04）。
本研究结果提供了 TS 多态性与 tHcy 浓度之间存在关联的证据。
