Variability within α- and β-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge

Objectives To investigate the association between polymorphic variation in α- and β-adrenoreceptor genes and cardiovascular activity at rest and in response to psychological challenge in a sample in which the heritability of these cardiovascular phenotypes may be established. Methods Several common polymorphisms were characterized within ADRA1B (α 1B ), ADRA2A (α 2A ), ADRB1 (β 1 ) and ADRB2 (β 2 ) and examined in relation to heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure, both at rest and in response to stress. Participants were 309 European-American, young adult men and women (including 101 monozygotic and 44 dizygotic twin pairs). Results In the full sample, participants carrying any G allele at base pair (bp) 1165 in ADRB1 exhibited elevated resting SBP and DBP and a larger DBP response to mental challenge compared to homozygotes for the C allele (P< 0.04). An AA genotype at bp 145 in ADRB1 was also associated with higher resting SBP and DBP than AG or GG genotypes (P < 0.03). At bp 46 in ADRB2, GG homozygotes had higher resting DBP than subjects possessing any A allele (P< 0.05). For the same polymorphism, however, AG heterozygotes showed lower SBP than both AA and GG homozygotes (P< 0.05). In a subsample of genetically unrelated individuals, ADRB1 (1165) continued to predict resting SBP, DBP and DBP response to stress (P < 0.03), while ADRB2 (46) was associated with resting SBP (P < 0.04) but not DBP. Finally, the degree of allele sharing at ADRB1 (1165) also predicted variability in SBP and DBP at rest among dizygotic twin pairs (P< 0.04). Conclusions These results indicate that some polymorphic variation within adrenoreceptor genes contributes to interindividual variability in resting SBP and DBP and in DBP response to mental challenge.