Determination of the Effects of eNOS Gene Polymorphisms (T-786C and Glu298Asp) on Nitric Oxide Levels in a Methylmercury-Exposed Population

Abstract

Nitric oxide (NO) is a potent vasodilator with multiple protective effects involved in the regulation of cardiovascular functions. Endothelial NO synthase (eNOS) gene polymorphisms and environmental factors, such as mercury (Hg) exposure, may influence NO levels and increase the risk of cardiovascular damage. The aim of this study was to determine the role of the T-786C and Glu298Asp polymorphisms of the eNOS gene on nitrite concentrations following Hg exposure in humans. It was postulated that Hg exposure might decrease circulating nitrite concentrations and that variants in the eNOS gene might enhance the adverse effects of Hg resulting in increased risk of cardiovascular disease. Blood samples were collected from 202 volunteers exposed to methylmercury (MeHg) following fish consumption. Blood Hg concentrations (BHg) were determined by inductively coupled plasma-mass spectrometry and nitrite plasma concentration by a chemiluminescent method. The mean Hg concentration was 50.5 ± 35.4 μg/L and mean nitrite concentration was 251.4 ± 106.3 nM. There were no significant differences in age, arterial blood pressure, body mass index, heart rate, and concentrations of Hg and nitrite concentrations between the genotype groups . When data were grouped together (TC + CC and TT group), there were still no marked differences. A multiple regression model indicated that decreased NO production was predominantly due to Hg, age, and gender. Polymorphisms did not seem to influence this effect. Our findings suggest that eNOS gene polymorphisms (T-786C and Glu298Asp) are not associated with an increased risk for cardiovascular diseases in MeHg-exposed subjects.

Recent Advances in Mercury Research

“…Two studies examined the contribution of MeHg to cardiovascular disease and found that polymorphisms in eNOS were not associated with increased risk of cardiovascular disease; however, a polymorphism in intron 4 increased susceptibility to cardiovascular disease after MeHg exposure by modulating NO levels [30, 32]. In addition, plasma eicosapentaenioic+docosahexaenoic acid or erythrocyte-mercury were not found to be associated with the risk of MI [30, 32].…”

“…In addition, plasma eicosapentaenioic+docosahexaenoic acid or erythrocyte-mercury were not found to be associated with the risk of MI [30, 32]. Future studies should aim to address the contribution of genetics and low-level mercury exposure to disease, taking into consideration the age of exposure and the age of testing.…”

“…Decreased nitric oxide (NO) production was attributed to mercury, age, and gender and was not influenced by gene polymorphisms. Their findings suggest that T-786C and Glu298Asp were not associated with an increased risk for cardiovascular diseases in MeHg-exposed subjects [30]. The same group investigated the contribution of the 27-nt tandem repeat of intron 4 of the eNOS gene on NO production, which could enhance susceptibility to cardiovascular disease in the MeHg-exposed study population.…”

Evaluation of GlutathioneS-transferaseGSTM1andGSTT1Polymorphisms and Methylmercury Metabolism in an Exposed Amazon Population

“…Several GSH-related enzymes are highly polymorphic, and epidemiological studies demonstrated that these polymorphisms may affect the metabolism of Hg (Goyer and Clarkson 2001;Gundacker et al 2010). Moreover, other studies were carried out concerning the relationship between other polymorphisms and adverse health effects induced by Hg exposure (de Marco et al 2011;Echeverria et al 2010;Heyer et al 2009). The GST genes, especially GSTM1 (mu) and T1 (theta), are important since they present a deletion that results in impaired catalytic activity associated with greater sensitivity to toxic compounds.…”

Mechanisms and modifiers of methylmercury-induced neurotoxicity

“…Polymorphisms did not seem to influence the decreased nitric oxide (NO) production as it was found to be predominantly due to Hg, age and gender. Their findings suggest that there is not an association between increased risk for cardiovascular disease in MeHg-exposed subjects and eNOS gene polymorphisms (T-786C and Glu298Asp) 84 . The same group investigated the contribution of the 27-nt tandem repeat of intron 4 of the eNOS gene to NO production, which could enhance susceptibility to cardiovascular disease in the MeHg-exposed study population.…”