Effects of polymorphisms in beta1-adrenoceptor and alpha-subunit of G protein on heart rate and blood pressure during exercise test. The Finnish Cardiovascular Study.
We tested whether the Arg389Gly and Ser49Gly polymorphisms of the beta1-adrenergic receptor gene ADRB1 and the T393C polymorphism of the G protein alpha-subunit gene GNAS1 modulate heart rate (HR) and blood pressure responses during an exercise stress test. The study population comprised 890 participants (563 men and 327 women, mean age 58.1 +/- 12.6 yr) of the Finnish Cardiovascular Study. Their HR, systolic (SAP), and diastolic arterial pressures (DAP) at rest, during exercise, and 4 min after the test were measured and analyzed by repeated-measurement ANOVA (RANOVA). Genotypes were detected by TaqMan 5' nuclease assay. In all subjects, and in men and women separately, the T393C of GNAS1 was the only polymorphism with genotype x time interaction in HR over the three study phases (P = 0.04, RANOVA). None of the polymorphisms presented genotype x time interaction in SAP or DAP responses (P > 0.10, RANOVA). In all subjects at rest, the Ser49Gly polymorphism of ADRB1 tended (P = 0.06, ANOVA) to differentiate HR. Arg389Gly polymorphism of ADRB1 affected maximal SAP during exercise (P = 0.04, ANOVA) and the change in SAP from rest to maximal (P = 0.03, ANOVA). Arg389 homozygotes, particularly men, were less likely to have ventricular extrasystoles during the exercise (odds ratio = 0.68, 95% confidence interval = 0.51-0.91, P = 0.009, and odds ratio = 0.60, 95% confidence interval = 0.42-0.86, P = 0.006, respectively) than did Gly389 carriers. In conclusion, polymorphisms examined appear to have modulatory effects on hemodynamics in a clinical exercise test setting. However, the effects in absolute numbers were minor and clinically possibly insignificant.
Nieminen
Tuomo
T
Dept. of Pharmacological Sciences, Medical School, Univ. of Tampere, Tampere FI-33014, Finland. tuomo.nieminen@iki.fi
Lehtimäki
Terho
T
Laiho
Jarno
J
Rontu
Riikka
R
Niemelä
Kari
K
Kööbi
Tiit
T
Lehtinen
Rami
R
Viik
Jari
J
Turjanmaa
Väinö
V
Kähönen
Mika
M
D000704:Analysis of Variance; D001794:Blood Pressure / Q000235:genetics; D005080:Exercise Test; D005260:Female; D005387:Finland; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D005838:Genotype; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*
D044385:GTP-Binding Protein alpha Subunits; D018342:Receptors, Adrenergic, beta-1