A common insertion/deletion polymorphism of the thymidylate synthase (TYMS) gene is a determinant of red blood cell folate and homocysteine concentrations.
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.
Kealey
Carmel
C
Department of Pharmacology, University of Pennsylvania School of Medicine, 153 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA.
Brown
Karen S
KS
Woodside
Jayne V
JV
Young
Ian
I
Murray
Liam
L
Boreham
Colin A
CA
McNulty
Helene
H
Strain
J J
JJ
McPartlin
Joseph
J
Scott
John M
JM
Whitehead
Alexander S
AS
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*
D020413:3' Untranslated Regions; D006710:Homocysteine; D005492:Folic Acid; D013940:Thymidylate Synthase