TY - JOUR
T1 - Catechol-O-methyltransferase genotype is associated with plasma total homocysteine levels and may increase venous thrombosis risk
AU - Gellekink, Henkjan
AU - Muntjewerff, Jan Willem
AU - Vermeulen, Sita H.H.M.
AU - Hermus, Ad R.M.M.
AU - Blom, Henk J.
AU - den Heijer, Martin
PY - 2007/12
Y1 - 2007/12
N2 - A disturbed methylation has been proposed as a mechanism via which homocysteine is associated with diseases like vascular disease, neural tube defects and mental disorders. Catechol-O-methyltransferase (COMT) is involved in the S-adenosyl-methionine-dependent methylation of catecholamines and cate-cholestrogens and in this way contributes to homocysteine synthesis. COMT dysfunction has been related to schizophrenia and breast cancer. We hypothesized that COMT dysfunction by virtue of functional genetic polymorphisms may affect plasma total homocysteine (tHcy). Our primary objective was to study the association between common COMT polymorphisms and tHcy. Secondly, we evaluated these polymorphisms as a risk factor for recurrent venous thrombosis. We obtained genotype data from four polymorphisms in the COMT gene (rs2097603, rs4633, rs4680 [324G>A] and rs 174699) from 401 population-based controls. We performed haplotype analysis to investigate the association between common haplotypes and tHcy. In addition, we assessed the rs4680 variant as a genetic risk factor in a case-control study on recurrent venous thrombosis (n= 169). We identified a common haplotype that was significantly associated with tHcy levels. This effect was largely explained by the rs4680 variant, resulting in an increase in tHcy of 10.4% (95% Cl 0.01 to 0.21, p=0.03) for 324AA compared with 324GG subjects. Interestingly, we found that the 324AA genotype was more common in venous thrombosis patients (OR 1.61 [95% Cl 0.97 to 2.65], p=0.06) compared to control subjects. We show that the COMT rs4680 variant modulates tHcy, and might be associated with venous thrombosis risk as well.
AB - A disturbed methylation has been proposed as a mechanism via which homocysteine is associated with diseases like vascular disease, neural tube defects and mental disorders. Catechol-O-methyltransferase (COMT) is involved in the S-adenosyl-methionine-dependent methylation of catecholamines and cate-cholestrogens and in this way contributes to homocysteine synthesis. COMT dysfunction has been related to schizophrenia and breast cancer. We hypothesized that COMT dysfunction by virtue of functional genetic polymorphisms may affect plasma total homocysteine (tHcy). Our primary objective was to study the association between common COMT polymorphisms and tHcy. Secondly, we evaluated these polymorphisms as a risk factor for recurrent venous thrombosis. We obtained genotype data from four polymorphisms in the COMT gene (rs2097603, rs4633, rs4680 [324G>A] and rs 174699) from 401 population-based controls. We performed haplotype analysis to investigate the association between common haplotypes and tHcy. In addition, we assessed the rs4680 variant as a genetic risk factor in a case-control study on recurrent venous thrombosis (n= 169). We identified a common haplotype that was significantly associated with tHcy levels. This effect was largely explained by the rs4680 variant, resulting in an increase in tHcy of 10.4% (95% Cl 0.01 to 0.21, p=0.03) for 324AA compared with 324GG subjects. Interestingly, we found that the 324AA genotype was more common in venous thrombosis patients (OR 1.61 [95% Cl 0.97 to 2.65], p=0.06) compared to control subjects. We show that the COMT rs4680 variant modulates tHcy, and might be associated with venous thrombosis risk as well.
KW - Catechol-O-methyltransferase
KW - Haplotype
KW - Homocysteine
KW - Venous thrombosis
UR - http://www.scopus.com/inward/record.url?scp=36949013216&partnerID=8YFLogxK
U2 - https://doi.org/10.1160/TH07-05-0381
DO - https://doi.org/10.1160/TH07-05-0381
M3 - Article
C2 - 18064318
SN - 0340-6245
VL - 98
SP - 1226
EP - 1231
JO - Thrombosis and haemostasis
JF - Thrombosis and haemostasis
IS - 6
ER -