title: Intron 4 polymorphism of the endothelial nitric oxide synthase (eNOS) gene is associated with decreased NO production in a mercury-exposed population.
abstract: Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a potent vasodilator and plays a prominent role in regulating the cardiovascular system. Decreased basal NO release may predispose to cardiovascular diseases. Evidence suggests that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene may regulate eNOS expression. On the other hand, some recent reports strongly suggest an association between methylmercury (MeHg) exposures and altered NO synthesis. In the present study, we investigate the contribution of the 27-pb tandem repeat polymorphism on nitric oxide production, which could enhance susceptibility to cardiovascular disease in the MeHg-exposed study population. Two-hundred-two participants (98 men and 104 women), all chronically exposed to MeHg through fish consumption were examined. Mean blood Hg concentration and nitrite plasma concentration were 50.5 ± 35.4 μg/L and 251.4 ± 106.3n M, respectively. Mean systolic and diastolic blood pressure were 120.1 ± 19.4mm Hg and 72.0 ± 10.6mm Hg, respectively. Mean body mass index was 24.5 ± 4.3 kg/m(2) and the mean heart rate was 69.8 ± 11.8 bpm. There were no significant differences in age, arterial blood pressure, body mass index or cardiac frequency between genotype groups (all P>0.05). However, we observed different nitrite concentrations in the genotypes groups, with lower nitrite levels for the 4a4a genotype carriers. Age, gender and the presence of intron 4 polymorphism contributed to nitrite reduction as a result of blood Hg concentration. Taken together, our results show that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene increases susceptibility to cardiovascular diseases after MeHg exposure by modulating nitric oxide levels.
authors: Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors: Katia Cristina
authors: KC
authors: de Marco
authors: Lusania Maria Greggi
authors: LM
authors: Antunes
authors: Jose Eduardo
authors: JE
authors: Tanus-Santos
authors: Fernando
authors: F
authors: Barbosa
mesh_terms: D000367:Age Factors; D000818:Animals; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000235:genetics*; D005260:Female; D005399:Fishes / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006339:Heart Rate; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008767:Methylmercury Compounds / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009573:Nitrites / Q000097:blood; D011110:Polymorphism, Genetic / Q000235:genetics*; D017747:Seafood / Q000633:toxicity*; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D006454:Hemoglobins; D008767:Methylmercury Compounds; D009573:Nitrites; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III