title: A common insertion/deletion polymorphism of the thymidylate synthase (TYMS) gene is a determinant of red blood cell folate and homocysteine concentrations.
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 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.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA.
authors.forename: Carmel
authors.initials: C
authors.lastname: Kealey
authors.forename: Karen S
authors.initials: KS
authors.lastname: Brown
authors.forename: Jayne V
authors.initials: JV
authors.lastname: Woodside
authors.forename: Ian
authors.initials: I
authors.lastname: Young
authors.forename: Liam
authors.initials: L
authors.lastname: Murray
authors.forename: Colin A
authors.initials: CA
authors.lastname: Boreham
authors.forename: Helene
authors.initials: H
authors.lastname: McNulty
authors.forename: J J
authors.initials: JJ
authors.lastname: Strain
authors.forename: Joseph
authors.initials: J
authors.lastname: McPartlin
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Whitehead
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012907:Smoking; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D006710:Homocysteine; D005492:Folic Acid; D013940:Thymidylate Synthase