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 alpha- and beta-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 (alpha(1B)), ADRA2A (alpha(2A)), ADRB1 (beta(1)) and ADRB2 (beta(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 (11165) 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. (C) 2002 Lippincott Williams Wilkins.