Novel Gene Variant Associated with Exercise Pressor Reflex Responsiveness

Abstract

PURPOSE: Activation of thinly myelinated and unmyelinated afferents innervating contracting skeletal muscle elicits the exercise pressor reflex. We hypothesized that single nucleotide polymorphisms (SNPs) of genes encoding ionotropic and metabotropic receptors commonly found on skeletal muscle afferents might account for part of the typical variation in blood pressure responses to exercise. METHODS: 101 healthy, college age, men and women of European ancestry participated. Multivariate modeling of the mean arterial pressure response to post-exercise circulatory arrest following 3-min of static handgrip exercise (30% of maximum) was used to stratify subjects into quartiles. Subjects from the highest (N=33) and lowest (N=25) quartiles provided buccal mucosa cells. DNA was extracted, amplified, and analyzed for common (minor allele frequency >20%), non-synonymous SNPs of genes with functional associations to autonomic disorders. We evaluated selected variants of the TRP (N=18), ASIC (N=3) and P2X (N=4) receptor families (real-time PCR, custom OpenArray™) and used contingency table analysis to compare the frequency of homozygotes and trait allele carriers between the two groups. RESULTS: Trait allele carriers of rs8065080, a T-to-C missense mutation of TRPV1, were more frequent in the high response group (73% vs 48%, P<0.1). Frequencies of all other SNPs did not differ between groups. CONCLUSIONS: Data from this pilot investigation suggest that intra-subject variation in mean arterial pressure during post-exercise circulatory arrest may associate with SNPs of genes putatively linked to the metabolic component of the exercise pressor reflex. Additional work is warranted to confirm these observations and explore the mechanistic role of TRP channels in exercise pressor reflex responsiveness. Supported in part by the Huck Institutes of the Life Sciences and the College of Health and Human Development.