title: The presence of the NOS3 gene polymorphism for intron 4 mitigates the beneficial effects of exercise training on ambulatory blood pressure monitoring in adults.
abstract: The number of studies that have evaluated exercise training (ET) and nitric oxide synthase (NOS)3 gene polymorphisms is scarce. The present study was designed to evaluate the relationship between exercise training and NOS3 polymorphisms at -786T>C, 894G>T, and intron 4b/a on blood pressure (BP) using 24-h ambulatory BP monitoring (ABPM), nitrate/nitrite levels (NOx), and redox state. Eighty-six volunteers (51 ± 0.6 yr old) were genotyped into nonpolymorphic and polymorphic groups for each of the three positions of NOS3 polymorphisms. Auscultatory BP, ABPM, SOD activity, catalase activity, NOx levels, and malondialdehyde levels were measured. DNA was extracted from leukocytes, and PCR followed by sequencing was applied for genotype analysis. Aerobic ET consisted of 24 sessions for 3 days/wk for 40 min at moderate intensity. This study was performed in a double-blind and crossover format. ET was effective in lowering office BP (systolic BP: 3.2% and diastolic BP: 3%) as well as ABPM (systolic BP: 2% and diastolic BP: 1.3%). Increased SOD and catalase activity (42.6% and 15.1%, respectively) were also observed. The NOS3 polymorphism for intron 4 mitigated the beneficial effect of ET for systolic BP (nonpolymorphic group: -3.0% and polymorphic group: -0.6%) and diastolic BP (nonpolymorphic group: -3.2% and polymorphic group: -0.5%), but it was not associated with NOx level and redox state. Paradoxical responses were found for positions T786-C and G894T for the NOS3 gene. Consistently, the presence of the polymorphism for intron 4 blunted the beneficial effects of ET in middle-aged adults. Possibly, this effect might be as consequence of intron 4 acting as a short intronic repeat RNA controlling endothelial NOS activity epigenetically.
authors.affiliation: Laboratory of Cardiovascular Physiology and Exercise Science, University of São Paulo State, Rio Claro, São Paulo, Brazil; and.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Sponton
authors.affiliation: Laboratory of Cardiovascular Physiology and Exercise Science, University of São Paulo State, Rio Claro, São Paulo, Brazil; and.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Esposti
authors.affiliation: Laboratory of Molecular Evolution, Institute of Bioscience, University of São Paulo State, Rio Claro, São Paulo, Brazil.
authors.forename: Cynara M
authors.initials: CM
authors.lastname: Rodovalho
authors.affiliation: Laboratory of Cardiovascular Physiology and Exercise Science, University of São Paulo State, Rio Claro, São Paulo, Brazil; and.
authors.forename: Maycon J
authors.initials: MJ
authors.lastname: Ferreira
authors.affiliation: Laboratory of Cardiovascular Physiology and Exercise Science, University of São Paulo State, Rio Claro, São Paulo, Brazil; and.
authors.forename: Aline P
authors.initials: AP
authors.lastname: Jarrete
authors.affiliation: Laboratory of Cardiovascular Physiology and Exercise Science, University of São Paulo State, Rio Claro, São Paulo, Brazil; and.
authors.forename: Chadi P
authors.initials: CP
authors.lastname: Anaruma
authors.affiliation: Laboratory of Molecular Evolution, Institute of Bioscience, University of São Paulo State, Rio Claro, São Paulo, Brazil.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Bacci
authors.affiliation: Laboratory of Cardiovascular Physiology and Exercise Science, University of São Paulo State, Rio Claro, São Paulo, Brazil; and azanesco@rc.unesp.br.
authors.forename: Angelina
authors.initials: A
authors.lastname: Zanesco
mesh_terms: D000483:Alleles; D001794:Blood Pressure / Q000502:physiology*; D018660:Blood Pressure Monitoring, Ambulatory; D002374:Catalase / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D002374:Catalase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase
keywords: blood pressure; exercise training; intron 4; nitric oxide synthase 3 polymorphisms