While the purpose of this study was to evaluate the effect of genetic polymorphisms, the overall goal was to examine associations between variation in the presynaptic NET and behavioral-disease associations. Methods and Findings We performed a sample of 4,006 healthy individuals (mean age, 28.6 [±6.9] years) with a comprehensive phenotypic and genotypic data set that included a genotype score based on 5,742 SNPs and the presynaptic NET genotype. The genetic association for BP was assessed by assessing the joint effect of the 5 SNPs and genotype on BP (i.e., the combination between gene × SNP interaction and genotype × SNP interaction estimates) using a linear regression model with a logic link function for BP. The genotype estimates showed significantly greater BP associated with SNP rs10764449, an SNP in the NET that is related to blood pressure. SNP rs10764449 is also associated with blood pressure, but does not measure hypertension. Genetic variation associated with the catecholamine hydroxybutyrate (John) response (n = 613) was assessed using the John response (R2), which includes a measure of John response to caffeine, the John response to alcohol, and alcohol response combined. The effects of genes on the 5 SNPs, rs10764449 or the R2, were assessed by computing each SNP's association with the John response and the genetic association with John response via linear regression, adjusting for the other 2 SNPs. A significant genetic association between BP and John response was found (petaohm R2 = .18). Associations between genes and John, the John response, and blood pressure were robust (r2 > .98). The 5 SNPs with most effect sizes were rs1801096, rs4100816, rs767819 and rs10937418. Conclusions We suggest that an altered NET activity reflects variation in blood pressure and John response to exercise.
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Original article 171 Genetic variation in the presynaptic norepinephrine transporter is associated with blood pressure responses to exercise in healthy humans Stars Kohl, e, Maureen K. Hanna, f, g,
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