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

Carmel Kealey, Karen S. Brown, Jayne V. Woodside, Ian Young, Liam Murray, Colin A. Boreham, Helene McNulty, J. J. Strain, Joseph McPartlin, John M. Scott, Alexander S. Whitehead

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 μg/l) compared with either ins/ins (282 μg/l) or ins/del (298 μg/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.

Original languageEnglish
Pages (from-to)347-353
Number of pages7
JournalHuman Genetics
Volume116
Issue number5
DOIs
Publication statusPublished - 1 Apr 2005

Fingerprint Dive into the research topics of 'A common insertion/deletion polymorphism of the thymidylate synthase (TYMS) gene is a determinant of red blood cell folate and homocysteine concentrations'. Together they form a unique fingerprint.

Cite this