Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Physiol Genomics. 2013 Feb 15;45(4):138-50. doi: 10.1152/physiolgenomics.00037.2012. Epub 2012 Dec 26.
Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation.
血压（BP）是一种动态表型，会迅速变化以适应环境条件的变化。直立是最近进化而来的特征，影响体位适应的遗传因素可能导致 BP 变异性。我们研究了体位对 BP 和中间 BP 表型遗传的影响。我们纳入了 64 个家系中的 384 对同胞，这些家系通过早发高血压和血脂异常进行了确定。血压、三个血流动力学和七个神经内分泌中间 BP 表型在仰卧和直立时进行测量。在全同胞中研究了体位对遗传力和遗传协方差估计的影响。通过同胞对分析对 196 个候选基因进行连锁分析，并获得了经验性显著估计值。实施了置换算法来研究体位对连锁的影响。ADRA1A、APO、CAST、CORIN、CRHR1、EDNRB、FGF2、GC、GJA1、KCNB2、MMP3、NPY、NR3C2、PLN、TGFBR2、TNFRSF6 和 TRHR 在仰卧位显示出与任何表型的连锁证据，而不是在直立位。AKR1B1、CD36、EDNRA、F5、MMP9、PKD2、PON1、PPARG、PPARGC1A、PRKCA 和 RET 则与直立位表型特异性连锁。进行了基因谱分析，以显示中间 BP 表型和每个体位特异性基因之间的遗传相互作用。当研究人员仅在单一体位上进行遗传研究时，BP 的重要遗传成分会被遗漏。仰卧位和直立位 BP 具有不同的遗传特征。标准化操作会影响到 BP 遗传研究的结果，从而反映其动态调节。
