Nieminen Tuomo, Lehtimäki Terho, Laiho Jarno, Rontu Riikka, Niemelä Kari, Kööbi Tiit, Lehtinen Rami, Viik Jari, Turjanmaa Väinö, Kähönen Mika
Dept. of Pharmacological Sciences, Medical School, Univ. of Tampere, Tampere FI-33014, Finland.
J Appl Physiol (1985). 2006 Feb;100(2):507-11. doi: 10.1152/japplphysiol.00899.2005. Epub 2005 Oct 6.
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.
我们检测了β1 - 肾上腺素能受体基因ADRB1的Arg389Gly和Ser49Gly多态性以及G蛋白α亚基基因GNAS1的T393C多态性是否会在运动应激试验期间调节心率(HR)和血压反应。研究人群包括芬兰心血管研究的890名参与者(563名男性和327名女性,平均年龄58.1±12.6岁)。通过重复测量方差分析(RANOVA)测量并分析了他们在静息、运动期间以及试验后4分钟时的心率、收缩压(SAP)和舒张压(DAP)。通过TaqMan 5'核酸酶测定法检测基因型。在所有受试者以及分别在男性和女性中,GNAS1的T393C是在三个研究阶段中唯一在心率方面存在基因型×时间交互作用的多态性(P = 0.04,RANOVA)。在收缩压或舒张压反应中,没有任何多态性表现出基因型×时间交互作用(P > 0.10,RANOVA)。在所有静息受试者中,ADRB1的Ser49Gly多态性有使心率产生差异的趋势(P = 0.06,ANOVA)。ADRB1的Arg389Gly多态性影响运动期间的最大收缩压(P = 0.04,ANOVA)以及收缩压从静息到最大值的变化(P = 0.03,ANOVA)。与Gly389携带者相比,Arg389纯合子,尤其是男性,在运动期间发生室性期前收缩可能性较小(优势比分别为0.68,95%置信区间 = 0.51 - 0.91,P = 0.009,以及优势比为0.60,95%置信区间 = 0.42 - 0.86,P = 0.006)。总之,在临床运动试验环境中,所检测的多态性似乎对血流动力学有调节作用。然而,绝对数值上的影响较小,在临床上可能无显著意义。