NOS3 Variants, Physical Activity, and Blood Pressure in the European Youth Heart Study

BACKGROUND In this study, we examined the influence of genetic variation in NOS3 on resting blood pressure (BP) in children and adolescents from the European Youth Heart Study (EYHS). Because the NOS3 gene expression is altered by physical activity (PA), we also tested for interaction between habitual PA and NOS3 variants on BP. METHODS A cross-sectional, random sample of 8-10-year old children (n = 1,214) and 14-16-year old adolescents (n = 1,141) from Denmark and Estonia were genotyped for four NOS3 tagging polymorphisms (rs1800783, rs1799983 (Glu298Asp), rs3918227, rs743507). PA was measured objectively using a hip-mounted accelerometer and through self-reported bicycling and TV-viewing. Permutation testing was used to correct for multiple testing, yielding an a level of 0.006. RESULTS Glu298Asp showed age-group-dependent associations with BP. In adolescents, Asp298 allele homozygotes had 0.19 s.d. (95% confidence interval (CI): 0.06; 0.13, P = 0.004) higher diastolic BP (DBP) and 0.25 s.d. (95% CI: 0.05; 0.46, P = 0.015) higher systolic BP (SBP), compared to Glu298 allele carriers. None of the three other single-nucleotide polymorphisms (SNPs) were associated with BP in adolescents. In children, none of the SNPs were associated with BP. No evidence of interaction between Glu298Asp and objectively measured PA was observed. Both self-reported bicycling and TV-viewing nominally modified the association between Glu298Asp and BP in adolescents (P <0.05), the genetic effect being most apparent in inactive individuals. However, none of the interactions persisted after correcting for multiple testing. CONCLUSIONS The NOS3 Glu298Asp variant may associate with resting BP in adolescence but not in childhood, an effect that could be modified by PA.