A common insertion/deletion polymorphism of the thymidylate synthase (TYMS) gene is a determinant of red blood cell folate and homocysteine concentrations

Hum Genet. 2005 Apr;116(5):347-53. doi: 10.1007/s00439-004-1243-2. Epub 2005 Jan 29.


Substantial evidence suggests that a low folate/high homocysteine phenotype is pathogenic. We analyzed the impact of the thymidylate synthase (TYMS) 3'UTR ins/del polymorphism on folate and homocysteine levels and assessed the relationship between the TYMS 3'UTR ins/del polymorphism and key genetic and lifestyle variables. Among non-smokers only, the TYMS 3'UTR ins/del polymorphism was significantly associated with red blood cell folate (RBC folate; P=0.002) and homocysteine (P=0.03) concentrations. Median RBC folate concentration was much higher for TYMS 3'UTR del/del subjects (434 microg/l) compared with either ins/ins (282 microg/l) or ins/del (298 microg/l) subjects. The median homocysteine concentration for del/del homozygotes was considerably lower compared with either ins/ins homozygotes or ins/del heterozygotes. A possible additive effect for the impact of the TYMS 3'UTR del/del and MTHFR 677CC genotypes on RBC folate concentration was also observed. Our findings suggest that the TYMS 3'UTR del/del genotype is a significant determinant of elevated RBC folate concentration in a non-smoking population of northwestern European adults and that this genotype confers protection against diseases for which a low folate/high homocysteine phenotype appears to be an etiologic component.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Erythrocytes / metabolism
  • Female
  • Folic Acid / blood*
  • Genotype
  • Homocysteine / blood*
  • Humans
  • Male
  • Polymorphism, Genetic*
  • Smoking*
  • Thymidylate Synthase / genetics*


  • 3' Untranslated Regions
  • Homocysteine
  • Folic Acid
  • Thymidylate Synthase