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The 894 G > T variant of endothelial nitric oxide synthase (eNOS) increases the risk of recurrent venous thrombosis through interaction with elevated homocysteine levels
Author(s) -
Heil S. G.,
Den Heijer M.,
Van Der RijtPisa B. J. M.,
Kluijtmans L. A. J.,
Blom H. J.
Publication year - 2004
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2004.00701.x
Subject(s) - enos , hyperhomocysteinemia , medicine , homocysteine , odds ratio , venous thrombosis , thrombosis , gastroenterology , cardiology , endocrinology , nitric oxide , nitric oxide synthase
Summary. 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.