Roy-Gagnon Marie-Hélène, Weir Matthew R, Sorkin John D, Ryan Kathleen A, Sack Paul A, Hines Scott, Bielak Lawrence F, Peyser Patricia A, Post Wendy, Mitchell Braxton D, Shuldiner Alan R, Douglas Julie A
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
J Hypertens. 2008 Apr;26(4):729-36. doi: 10.1097/HJH.0b013e3282f524b4.
Blood pressure (BP) response to the cold pressor test (CPT) has been found to predict the development of hypertension and cardiovascular disease in prospective studies. The determinants of BP response to the CPT, including the role of genetic factors, however, are largely unknown. Additionally, to our knowledge, no study has examined the genetics of BP recovery from the CPT, including whether shared genetic factors influence both reactivity and recovery.
As part of the Heredity and Phenotype Intervention Heart Study, we administered a 2.5 min hand CPT to 835 participants from 18 extended Amish families. We estimated the heritability of BP reactivity and recovery (measured by the incremental area under the curve) and the genetic correlations between baseline, reactivity, and recovery BP phenotypes.
After adjusting for relevant covariates, including baseline BP, the heritability estimates for both systolic BP (SBP) and diastolic BP (DBP) reactivity and recovery differed significantly from zero (P < 0.01), with 12-25% of the total variation in BP response attributable to additive genetic effects. The genetic correlations between baseline DBP and response phenotypes were not significantly different from zero, whereas the genetic correlation between DBP reactivity and recovery (0.74) was significantly different from zero and 1 (P < 0.005). The genetic correlation between SBP reactivity and recovery was similar (0.81; P < 0.05).
We conclude that, independent of baseline BP, BP response to CPT is heritable, and that both shared and unshared genetic factors influence BP reactivity and recovery, thus stressing the importance of identifying genetic variants that influence both traits.
在前瞻性研究中发现，血压（BP）对冷加压试验（CPT）的反应可预测高血压和心血管疾病的发生。然而，BP对CPT反应的决定因素，包括遗传因素的作用，在很大程度上尚不清楚。此外，据我们所知，尚无研究探讨CPT后血压恢复的遗传学，包括是否有共同的遗传因素影响反应性和恢复。
作为遗传与表型干预心脏研究的一部分，我们对来自18个阿米什大家庭的835名参与者进行了2.5分钟的手部CPT。我们估计了血压反应性和恢复（通过曲线下增量面积测量）的遗传力，以及基线、反应性和恢复血压表型之间的遗传相关性。
在调整包括基线血压在内的相关协变量后，收缩压（SBP）和舒张压（DBP）反应性及恢复的遗传力估计值均显著不同于零（P < 0.01），血压反应总变异的12 - 25%可归因于加性遗传效应。基线DBP与反应表型之间的遗传相关性与零无显著差异，而DBP反应性与恢复之间的遗传相关性（0.74）显著不同于零和1（P < 0.005）。SBP反应性与恢复之间的遗传相关性相似（0.81；P < 0.05）。
我们得出结论，独立于基线血压，BP对CPT的反应具有遗传性，并且共同和非共同的遗传因素均影响BP反应性和恢复，从而强调了识别影响这两个性状的基因变异的重要性。
