Thymidylate synthase: a novel genetic determinant of plasma homocysteine and folate levels

Hum Genet. 2002 Sep;111(3):299-302. doi: 10.1007/s00439-002-0779-2. Epub 2002 Jul 26.


The thymidylate synthase gene ( TYMS or TS) encodes a tightly regulated enzyme that catalyzes the conversion of deoxyuridylate to thymidylate, and contains a tandem repeat polymorphism that affects expression of the enzyme. We have investigated the relationship between TYMS genotype and plasma concentrations of homocysteine and folate in a cohort of 505 Chinese from Singapore. TYMS 3/3 genotype was associated with reduced plasma folate and, among individuals with low dietary folate intake, with elevated plasma homocysteine levels. These associations were independent of the well-established methylenetetrahydrofolate reductase ( MTHFR) C677T genotype effects on plasma folate and homocysteine levels. Our results suggest that TYMS and MTHFR compete for limiting supplies of folate required for the remethylation of homocysteine. These genetic determinants of plasma folate and homocysteine levels may be useful in identifying individuals at increased risk for cardiovascular disease.

MeSH terms

  • Cohort Studies
  • Female
  • Folic Acid / blood*
  • Gene Frequency
  • Genotype
  • Homocysteine / blood*
  • Humans
  • Male
  • Methylation
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism
  • Thymidylate Synthase / genetics*
  • Thymidylate Synthase / metabolism


  • Homocysteine
  • Folic Acid
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Thymidylate Synthase