Influence of thymidylate synthase gene polymorphisms on total plasma homocysteine concentrations

Background: 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. Purpose: The purpose of this research was to investigate the relationship between TS polymorphisms and total plasma homocysteine (tHcy) levels. Methods: 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. Results: 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). Conclusions: The findings of this research provide evidence of an association between TS polymorphisms and tHcy concentrations. (C) 2010 Elsevier Inc. All rights reserved.