title: Association between physical activity and blood pressure is modified by variants in the G-protein coupled receptor 10.
abstract: Hypertension is strongly related to cardiovascular disease and all-cause mortality. Exercise reduces blood pressure but the response varies between individuals. The mechanisms by which physical activity energy expenditure (PAEE) modifies blood pressure are not fully defined but include modulation of sympathetic tone. Novel polymorphisms in the G-protein coupled receptor (GPR10) have been linked with high blood pressure. GPR10 may mediate the relationship between PAEE and blood pressure via central nervous mechanisms. We examined whether two GPR10 polymorphisms (G-62A and C914T) modify the association between PAEE and blood pressure in the MRC Ely study (N=687). When stratified by the C914T genotype, there were between-group differences for body mass index (BMI) (P=0.05), diastolic blood pressure (DBP) (P=0.006), and systolic blood pressure (SBP) (P=0.005). No differences were found between G-62A genotypes. The previously reported inverse relationship between PAEE and blood pressure was not observed in minor allele carriers for either polymorphism (A62 carriers: DBP beta-1.11, P=0.52; SBP beta-1.66, P=0.52. T914 carriers: SBP beta=3.27; P=0.60) but was in common allele homozygotes (G62G: DBP beta-6.18 P=0.00001; SBP beta-8.54 P=0.0001. C914C: SBP beta-7.07; P=0.00001). This corresponded to a significant interaction between PAEE and GPR10 polymorphisms on DBP (G-62A: P=0.006) and SBP (G-62A: P=0.008. C914T: P=0.068). Significant interactions were observed between haplotype (derived from G-62A and C914T), PAEE, and blood pressure (DBP: P=0.08; SBP: P=0.023). The effect of physical activity on blood pressure is highly variable at population level. Knowledge of GPR10 genotype may define those who are least likely to benefit from physical activity. These findings may have relevance in the targeted treatment of hypertensive disease.
authors.affiliation: University of Cambridge, Department of Public Health and Primary Care, Cambridge, UK.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.forename: Sumit
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Jian'an
authors.initials: J
authors.lastname: Luan
authors.forename: Carl
authors.initials: C
authors.lastname: Montague
authors.forename: John
authors.initials: J
authors.lastname: Brennand
authors.forename: Benjamin
authors.initials: B
authors.lastname: Challis
authors.forename: Søren
authors.initials: S
authors.lastname: Brage
authors.forename: Ulf
authors.initials: U
authors.lastname: Ekelund
authors.forename: Rita P S
authors.initials: RP
authors.lastname: Middelberg
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: D001794:Blood Pressure / Q000235:genetics*; D004734:Energy Metabolism; D015444:Exercise; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C112345:PRLHR protein, human; D043562:Receptors, G-Protein-Coupled