TY - JOUR
T1 - Cystathionine β-synthase polymorphisms and hyperhomocysteinaemia
T2 - An association study
AU - Lievers, Karin J.A.
AU - Kluijtmans, Leo A.J.
AU - Heil, Sandra G.
AU - Boers, Godfried H.J.
AU - Verhoef, Petra
AU - den Heijer, Martin
AU - Trijbels, Frans J.M.
AU - Blom, Henk J.
N1 - Funding Information: This study was, in part, supported by grants 93.176 and 97.071 from the Netherlands Heart Foundation. Dr Leo AJ Kluijtmans is a post-doctoral fellow of the Netherlands Heart Foundation (D99.023) and Dr Henk J Blom is an Established Investigator of the Netherlands Heart Foundation (D97.021).
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Hyperhomocysteinaemia is generally accepted as an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. The only way of homocysteine degradation is conversion to cysteine in the transsulfuration pathway in which the regulating step is catalysed by cystathionine β-synthase (CBS). Mild impairment of CBS function could therefore affect homocysteine concentration, in particular after methionine loading, and consequently cardiovascular disease (CVD) risk. We analysed two silent polymorphisms and one short tandem repeat in the CBS gene (ie 699C→T, 1080C→T and -5697 (GT) STR) as genetic markers potentially in linkage disequilibrium with a functional polymorphism. We assessed their association with fasting and post-methionine load homocysteine in 190 patients with arterial occlusive disease, and in 381 controls. No differences in CBS genotype frequencies between cases and controls were found, nor was a particular CBS genotype associated with an elevated risk of arterial occlusive disease. Although we did find a high rate of linkage disequilibrium between the two single nucleotide polymorphisms and the GT STR, none of the genotypes defined by the three CBS variants studied showed an association with elevated fasting, post-load or increase upon methionine loading homocysteine concentrations. In conclusion, we did not find any indication that genetic variation in the CBS gene is associated with increased homocysteine concentrations.
AB - Hyperhomocysteinaemia is generally accepted as an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. The only way of homocysteine degradation is conversion to cysteine in the transsulfuration pathway in which the regulating step is catalysed by cystathionine β-synthase (CBS). Mild impairment of CBS function could therefore affect homocysteine concentration, in particular after methionine loading, and consequently cardiovascular disease (CVD) risk. We analysed two silent polymorphisms and one short tandem repeat in the CBS gene (ie 699C→T, 1080C→T and -5697 (GT) STR) as genetic markers potentially in linkage disequilibrium with a functional polymorphism. We assessed their association with fasting and post-methionine load homocysteine in 190 patients with arterial occlusive disease, and in 381 controls. No differences in CBS genotype frequencies between cases and controls were found, nor was a particular CBS genotype associated with an elevated risk of arterial occlusive disease. Although we did find a high rate of linkage disequilibrium between the two single nucleotide polymorphisms and the GT STR, none of the genotypes defined by the three CBS variants studied showed an association with elevated fasting, post-load or increase upon methionine loading homocysteine concentrations. In conclusion, we did not find any indication that genetic variation in the CBS gene is associated with increased homocysteine concentrations.
KW - Association study
KW - Cardiovascular disease
KW - Cystathionine β-synthase (CBS)
KW - Homocysteine
KW - Linkage disequilibrium
KW - Polymorphism
UR - http://www.scopus.com/inward/record.url?scp=0037269292&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/sj.ejhg.5200899
DO - https://doi.org/10.1038/sj.ejhg.5200899
M3 - Article
C2 - 12529702
SN - 1018-4813
VL - 11
SP - 23
EP - 29
JO - European journal of human genetics
JF - European journal of human genetics
IS - 1
ER -