A common silent single nucleotide polymorphism (393 T>C) in exon 5 of the guanine nucleotide-binding protein system α subunit (GNAS) gene associates with hypertension, and altered autonomic nervous system function and response to β-blockade. We examined the effects of GNAS 393 T>C on the acute post-exercise BP response among 48 Caucasian men (mean ± SEM, 43.7±1.4 yr) with hypertension (145.1±1.5/85.5±1.1 mmHg). Subjects self disclosed a family history of hypertension. Experiments were non-exercise control and 2 exercise bouts at 40% (LIGHT) and 60% (MODERATE) of peak oxygen uptake. Subjects left the laboratory with an ambulatory BP monitor. Genotypes were detected using polymerase chain reaction and restriction enzyme digestion. Repeated measure ANCOVA tested if BP differed over time among experiments and GNAS genotypes (n=37, TT/TC; n=11, CC). Systolic BP increased 8.0±3.6 mmHg less (p<0.05) and diastolic BP tended to decrease 5.1±2.8 mmHg more (p=0.076) after LIGHT vs. non-exercise control among men with the GNAS T393 allele than CC homozygotes. There were no genotype differences in BP after MODERATE vs. non-exercise control (p≥0.05). Most men with the GNAS T393 allele and a family history of hypertension had lower BP after LIGHT (18/20) vs. non-exercise control; whereas 64% of men with the GNAS CC genotype did not have lower BP after LIGHT (7/11), independent of family history of hypertension (p<0.01). Men with the GNAS T393 allele, a family history of hypertension, and high BP appear to experience the antihypertensive effects of lower intensity, aerobic exercise more so than men with the GNAS CC genotype.
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