Abstract
Thymidylate synthase (TYMS) and 5,10-methylenetetrahydrofolate reductase (MTHFR) may compete for their common cofactor 5,10-methylenetetrahyhdrofolate (5,10-meTHF). Limiting 5,10-meTHF results in elevated homocysteine, especially in individuals homozygous for the T allele of the MTHFR C677T polymorphism. The TYMS gene has a tandem repeat polymorphism (two repeats or three repeats, designated 2R or 3R, respectively), which may also affect homocysteine concentrations. The 3R allele is subject to increased translational efficiency in vitro and the 3R3R genotype is associated with both decreased serum folate and elevated plasma homocysteine (tHcy) in a population of Singapore Chinese. We assessed the relationship between TYMS genotype and key biochemical and genetic variables in a random sample of 392 healthy young Northwestern European men and women. The tHcy concentrations for 3R3R homozygotes (median 8.5 μmol/l) did not differ significantly from those for 2R2R homozygotes (median 8.7 μmol/l) or 2R3R heterozygotes (median 9.3 μmol/l) in the population as a whole (P=0.43), or in subsets of subjects with low serum folate (P=0.60) or the MTHFR 677TT genotype (P=0.90). Furthermore, there was no trend toward elevated tHcy in 3R3R homozygotes. Similarly, the TYMS tandem repeat polymorphism was not associated with serum folate concentrations. Our findings indicate that the TYMS 3R3R genotype is not a determinant of homocysteine in this sample of healthy young Caucasian adults from Northern Ireland.
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Acknowledgements
This work was supported by NIH grants AR47633 and HD39195. Karen S. Brown is supported by a grant from the American Heart Association and Leo A.J. Kluijtmans is supported by grant 1999T023 from the Netherlands Heart Foundation. Support for the Young Hearts Project has been provided by the British Heart Foundation and the Wellcome Trust.
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Brown, K.S., Kluijtmans, L.A.J., Young, I.S. et al. The thymidylate synthase tandem repeat polymorphism is not associated with homocysteine concentrations in healthy young subjects. Hum Genet 114, 182–185 (2004). https://doi.org/10.1007/s00439-003-1039-9
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DOI: https://doi.org/10.1007/s00439-003-1039-9