TY - JOUR
T1 - Associations of common polymorphisms in the thymidylate synthase, reduced folate carrier and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase genes with folate and homocysteine levels and venous thrombosis risk
AU - Gellekink, Henkjan
AU - Blom, Henk J.
AU - Den Heijer, Martin
N1 - Funding Information: This study was supported by Grant 2002B68 from the Netherlands Heart Foundation. Martin den Heijer is supported by a VENI grant from the Dutch Organization for Scientific Research (NWO). The authors gratefully acknowledge F. Philips, E. Cornelissen and D. Groen for excellent technical assistance.
PY - 2007/4/1
Y1 - 2007/4/1
N2 - Background: Folate is important in purine and thymidylate synthesis and, via homocysteine remethylation, facilitates S-adenosylmethionine-dependent transmethylation. Low folate availability leads to hyperhomocysteinemia, which is a risk factor for arterial vascular disease and venous thrombosis. Genetic variation in folate-metabolizing genes may affect folate availability and hence confer a greater risk of venous thrombosis. Methods: We genotyped the thymidylate synthase (TYMS) 28-bp repeat and 6-bp deletion, and the reduced folate carrier (RFC1) 80G>A and AICAR transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) 346C>G polymorphisms in population-based controls (n=431), and assessed their effect on plasma total homocysteine (tHcy), and serum and red blood cell (RBC) folate. We investigated the associations between these variants and disease risk in a retrospective case-control study on recurrent venous thrombosis (n=173) as well. Results: None of the genotypes, alone or in combination, were associated with major changes in tHcy. However, the TYMS 28-bp repeat was associated with serum and RBC folate levels. We found no evidence that the genetic variants studied were associated with recurrent venous thrombosis risk. Conclusions: The TYMS 28-bp repeat and 6-bp deletion, and RFC1 80G>A and ATIC 346C>G polymorphisms are not associated with tHcy, but we did observe an association between the TYMS 28-bp repeat and serum and RBC folate in a general population. None of the polymorphisms was associated with recurrent venous thrombosis risk.
AB - Background: Folate is important in purine and thymidylate synthesis and, via homocysteine remethylation, facilitates S-adenosylmethionine-dependent transmethylation. Low folate availability leads to hyperhomocysteinemia, which is a risk factor for arterial vascular disease and venous thrombosis. Genetic variation in folate-metabolizing genes may affect folate availability and hence confer a greater risk of venous thrombosis. Methods: We genotyped the thymidylate synthase (TYMS) 28-bp repeat and 6-bp deletion, and the reduced folate carrier (RFC1) 80G>A and AICAR transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) 346C>G polymorphisms in population-based controls (n=431), and assessed their effect on plasma total homocysteine (tHcy), and serum and red blood cell (RBC) folate. We investigated the associations between these variants and disease risk in a retrospective case-control study on recurrent venous thrombosis (n=173) as well. Results: None of the genotypes, alone or in combination, were associated with major changes in tHcy. However, the TYMS 28-bp repeat was associated with serum and RBC folate levels. We found no evidence that the genetic variants studied were associated with recurrent venous thrombosis risk. Conclusions: The TYMS 28-bp repeat and 6-bp deletion, and RFC1 80G>A and ATIC 346C>G polymorphisms are not associated with tHcy, but we did observe an association between the TYMS 28-bp repeat and serum and RBC folate in a general population. None of the polymorphisms was associated with recurrent venous thrombosis risk.
KW - Folate
KW - Homocysteine
KW - Polymorphisms
KW - Recurrent venous thrombosis
UR - http://www.scopus.com/inward/record.url?scp=34247326565&partnerID=8YFLogxK
U2 - https://doi.org/10.1515/CCLM.2007.091
DO - https://doi.org/10.1515/CCLM.2007.091
M3 - Article
C2 - 17439323
SN - 1434-6621
VL - 45
SP - 471
EP - 476
JO - Clinical chemistry and laboratory medicine
JF - Clinical chemistry and laboratory medicine
IS - 4
ER -