title: NOS3 Glu298Asp genotype and blood pressure response to endurance training: the HERITAGE family study.
abstract: Endothelium-dependent vasodilation is a mechanism that may affect blood pressure response to endurance training. Because NO plays a central role in this process, the endothelial NO synthase gene is a good candidate for the regulation of exercise blood pressure. We investigated the associations between an endothelial NO synthase gene polymorphism (Glu298Asp) and endurance training-induced changes in resting and submaximal exercise blood pressure in 471 white subjects of the HERITAGE Family Study. Two submaximal exercise tests at 50 W were conducted both before and after a 20-week endurance training program. Steady-state exercise blood pressure was measured twice in each test with an automated unit. The Glu298Asp polymorphism was typed with a PCR-based method and digestion with BAN:II. Both systolic and diastolic blood pressure at 50 W decreased in response to the training program, whereas resting blood pressure remained unchanged. The decrease in diastolic blood pressure at 50 W was greater (P=0.0005, adjusted for age, gender, baseline body mass index, and baseline diastolic blood pressure at 50 W) in the Glu/Glu homozygotes (4.4 [SEM 0.4] mm Hg, n=187) than in the heterozygotes (3.1 [0.4] mm Hg, n=213) and the Asp/Asp homozygotes (1.3 [0.7] mm Hg, n=71). The genotype accounted for 2.3% of the variance in diastolic blood pressure at 50 W training response. Both the Glu298 homozygotes and the heterozygotes had a greater (P=0.013) training-induced reduction in rate-pressure product at 50 W than the Asp298 homozygotes. These data suggest that DNA sequence variation in the endothelial NO synthase gene locus is associated with the endurance training-induced decreases in submaximal exercise diastolic blood pressure and rate-pressure product in sedentary normotensive white subjects.
authors.affiliation: Pennington Biomedical Research Center, Human Genomics Laboratory, Baton Rouge, LA, USA. rankint@pbrc.edu
authors.forename: T
authors.initials: T
authors.lastname: Rankinen
authors.forename: T
authors.initials: T
authors.lastname: Rice
authors.forename: L
authors.initials: L
authors.lastname: Pérusse
authors.forename: Y C
authors.initials: YC
authors.lastname: Chagnon
authors.forename: J
authors.initials: J
authors.lastname: Gagnon
authors.forename: A S
authors.initials: AS
authors.lastname: Leon
authors.forename: J S
authors.initials: JS
authors.lastname: Skinner
authors.forename: J H
authors.initials: JH
authors.lastname: Wilmore
authors.forename: D C
authors.initials: DC
authors.lastname: Rao
authors.forename: C
authors.initials: C
authors.lastname: Bouchard
mesh_terms: D000328:Adult; D001483:Base Sequence / Q000235:genetics / Q000502:physiology; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D010641:Phenotype; D010807:Physical Endurance / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic
chemical_list: D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III