Endothelial Nitric Oxide Synthase Gene Polymorphisms Increase Risk of Deep Vein Thrombosis by Altering Homocysteine Levels.

Abstract

Deep Vein Thrombosis (DVT) is a multicausal disease involving both acquired as well as genetic factors. Nitric oxide is an influential endogenous factor having its role in the development of deep vein thrombosis. It maintains the vascular integrity and any alterations in its levels may lead to a thrombotic event. It may also modulate homocysteine metabolism to cause hyperhomocysteinemia, which is a prominent risk factor for thrombosis. The objective of the study was to study if endothelial nitric oxide gene polymorphisms, 894G/T, and 2479G/A alter the plasma nitric oxide and homocysteine levels which may eventually increase the risk of deep vein thrombosis. One hundred Doppler ultrasonography and computerized tomography confirmed (for cerebral venous thrombosis), non-related DVT patients (M:F = 58:42; age range = 18 to 61 years) served as the study population. Two hundred hospital staff and their relatives or unrelated attendants of the patients served as the controls. Nitric oxide levels were determined by measuring its metabolites (NOx), and EIA was used to measure homocysteine levels. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for detecting the eNOS polymorphisms 894G/T and 2479G/A. In total, DVT subjects have 25% higher plasma levels of homocysteine and 37% lower levels of NOx in their circulation when compared to controls. In tertile analysis of nitric oxide and homocysteine levels, 894G/T and 2479G/A polymorphisms were associated with plasma nitric oxide and homocysteine levels. The increased risk of deep vein thrombosis was associated with endothelial nitric oxide gene polymorphisms and nitric oxide levels, but homocysteine levels were not a risk for deep vein thrombosis. The present study demonstrates that 894G/T and 2479G/A polymorphisms interact with lower levels of nitric oxide and higher levels of homocysteine that may possess the risk of deep vein thrombosis.