title: Endothelial nitric oxide synthase polymorphisms and adaptation of parasympathetic modulation to exercise training.
abstract: OBJECTIVE
  There is a large interindividual variation in the parasympathetic adaptation induced by aerobic exercise training, which may be partially attributed to genetic polymorphisms. Therefore, we investigated the association among three polymorphisms in the endothelial nitric oxide gene (-786T>C, 4b4a, and 894G>T), analyzed individually and as haplotypes, and the parasympathetic adaptation induced by exercise training.
  
  
  METHODS
  Eighty healthy males, age 20-35 yr, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis, and haplotypes were inferred using the software PHASE 2.1. Autonomic modulation (i.e., HR variability and spontaneous baroreflex sensitivity) and peak oxygen consumption (VO(2peak)) were measured before and after training (running, moderate to severe intensity, three times per week, 60 min·day(-1), during 18 wk).
  
  
  RESULTS
  Training increased VO(2peak) (P < 0.05) and decreased mean arterial pressure (P < 0.05) in the whole sample. Subjects with the -786C polymorphic allele had a significant reduction in baroreflex sensitivity after training (change: wild type (-786TT) = 2% ± 89% vs polymorphic (-786TC/CC) = -28% ± 60%, median ± quartile range, P = 0.03), and parasympathetic modulation was marginally reduced in subjects with the 894T polymorphic allele (change: wild type (894GG) = 8% ± 67% vs polymorphic (894GT/TT) = -18% ± 59%, median ± quartile range, P = 0.06). Furthermore, parasympathetic modulation percent change was different between the haplotypes containing wild-type alleles (-786T/4b/894G) and polymorphic alleles at positions -786 and 894 (-786C/4b/894T) (-6% ± 56% vs -41% ± 50%, median ± quartile range, P = 0.04).
  
  
  CONCLUSIONS
  The polymorphic allele at position -786 and the haplotype containing polymorphic alleles at positions -786 and 894 in the endothelial nitric oxide gene were associated with decreased parasympathetic modulation after exercise training.
authors.affiliation: Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Brazil.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Silva
authors.forename: Fabricia J
authors.initials: FJ
authors.lastname: Neves
authors.forename: Marcelo V
authors.initials: MV
authors.lastname: Negrão
authors.forename: Cleber R
authors.initials: CR
authors.lastname: Alves
authors.forename: Rodrigo G
authors.initials: RG
authors.lastname: Dias
authors.forename: Guilherme B
authors.initials: GB
authors.lastname: Alves
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.forename: Maria U
authors.initials: MU
authors.lastname: Rondon
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Negrão
authors.forename: Antonio Claudio Lucas
authors.initials: AC
authors.lastname: DA Nóbrega
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000328:Adult; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D006239:Haplotypes; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D010101:Oxygen Consumption / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011110:Polymorphism, Genetic; D012420:Running / Q000502:physiology*; D055815:Young Adult
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III