ebb89a67-ecd4-4145-8100-a869bd20f1e9
title
The  894 G > T  variant of  endothelial nitric oxide synthase  ( eNOS ) increases the risk of recurrent venous thrombosis through interaction with elevated homocysteine levels.
8afaf1dd-7407-4949-ae6e-096e7a432306
abstract
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.