TY - JOUR
T1 - The 894 G > T variant of endothelial nitric oxide synthase (eNOS) increases the risk of recurrent venous thrombosis through interaction with elevated homocysteine levels
AU - Heil, S. G.
AU - Den Heijer, M.
AU - Van der Rijt-Pisa, B. J.M.
AU - Kluijtmans, L. A.J.
AU - Blom, Henk J.
PY - 2004/5
Y1 - 2004/5
N2 - Background: Venous thrombosis is a multicausal disease involving both genetic as well as acquired risk factors. Hyperhomocysteinemia is associated with a 2-fold increased risk of recurrent venous thrombosis (RVT). Recently, the 894 G > T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia. Objectives: We hypothesized an interrelation of hyperhomocysteinemia, the eNOS 894 G > T variant and RVT risk. Methods: The eNOS 894 G > T variant was studied in 170 cases with a history of RVT and 433 controls from the general population. Results: The eNOS 894 TT genotype may increase RVT risk [odds ratio (OR) 1.3 (0.7-2.6)], but no association of the eNOS 894 G > T variant with elevated homocysteine was found in controls. Interestingly, in RVT cases the coexistence of both the 894 TT genotype and elevated tHcy levels (> 90th percentile) was more frequently present than in controls, which led to a substantially increased risk of recurrent venous thrombosis [fasting tHcy OR 5.3 (1.1-24.1), postload tHcy OR 6.5 (1.6-29.5)]. Conclusion: The results of the present study demonstrate that the eNOS 894 G > T variation interacts with elevated tHcy levels, leading to an increased risk of recurrent thrombotic events. This interaction points in the direction of S-nitrosation as a mechanism by which homocysteine exerts its detrimental effects on the hemostatic system.
AB - Background: Venous thrombosis is a multicausal disease involving both genetic as well as acquired risk factors. Hyperhomocysteinemia is associated with a 2-fold increased risk of recurrent venous thrombosis (RVT). Recently, the 894 G > T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia. Objectives: We hypothesized an interrelation of hyperhomocysteinemia, the eNOS 894 G > T variant and RVT risk. Methods: The eNOS 894 G > T variant was studied in 170 cases with a history of RVT and 433 controls from the general population. Results: The eNOS 894 TT genotype may increase RVT risk [odds ratio (OR) 1.3 (0.7-2.6)], but no association of the eNOS 894 G > T variant with elevated homocysteine was found in controls. Interestingly, in RVT cases the coexistence of both the 894 TT genotype and elevated tHcy levels (> 90th percentile) was more frequently present than in controls, which led to a substantially increased risk of recurrent venous thrombosis [fasting tHcy OR 5.3 (1.1-24.1), postload tHcy OR 6.5 (1.6-29.5)]. Conclusion: The results of the present study demonstrate that the eNOS 894 G > T variation interacts with elevated tHcy levels, leading to an increased risk of recurrent thrombotic events. This interaction points in the direction of S-nitrosation as a mechanism by which homocysteine exerts its detrimental effects on the hemostatic system.
KW - Hyperhomocysteinemia
KW - Nitric oxide synthase
KW - Recurrent venous thrombosis
UR - http://www.scopus.com/inward/record.url?scp=13244278181&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/j.1538-7836.2004.00701.x
DO - https://doi.org/10.1111/j.1538-7836.2004.00701.x
M3 - Article
C2 - 15099281
SN - 1538-7933
VL - 2
SP - 750
EP - 753
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 5
ER -