University of Texas Health Science Center at San Antonio, Research Imaging Institute, San Antonio, TX 78284, USA.
Hypertension. 2011 Feb;57(2):330-5. doi: 10.1161/HYPERTENSIONAHA.110.162206. Epub 2010 Dec 6.
Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7 × 1.7 × 3 mm; 55 directions) diffusion tensor imaging data were analyzed for 332 (202 females; mean age 47.9 ± 13.3 years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements (pulse pressure, systolic BP, and diastolic BP) and fractional anisotropy (whole-brain and regional values). Intersubject variance in pulse pressure and systolic BP exhibited a significant genetic overlap with variance in whole-brain fractional anisotropy values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=-0.75; P=0.01). The pattern of genetic overlap between BP and WM integrity was generally in agreement with the pulse-wave encephalopathy theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development, suggesting a possible role for genotype-by-age interactions.
动脉脉搏压和血压（BP）升高可导致脑白质（WM）萎缩，这可能归因于共同的遗传因素。我们计算了 BP 与水扩散分数各向异性之间共享遗传方差的大小，后者是对具有明确定义的墨西哥裔美国人人群 WM 完整性的敏感测量。在脉冲波脑病理论的背景下，解释了 BP 与分数各向异性之间全脑和区域遗传重叠的模式。我们还测试了区域遗传多效性模式是否受 WM 发育的系统发育调节。对来自圣安东尼奥家族心脏研究的 332 名（202 名女性；平均年龄 47.9 ± 13.3 岁）成员的 BP 和高分辨率（1.7×1.7×3mm；55 个方向）扩散张量成像数据进行了分析。双变量遗传相关分析用于计算几个 BP 测量值（脉搏压、收缩压和舒张压）和分数各向异性（全脑和区域值）之间的遗传重叠。脉搏压和收缩压的个体间方差与全脑分数各向异性值的方差表现出显著的遗传重叠，分别共享 36%和 22%的遗传方差。在区域上，WM 发育的速度对共享遗传方差有显著影响（r=-0.75；P=0.01）。BP 与 WM 完整性之间遗传重叠的模式通常与脉冲波脑病理论一致。我们的研究提供了证据表明，一组具有多效性作用的遗传因素共同影响 BP 和 WM 完整性的表型变异。这种重叠的大小似乎受 WM 发育的系统发育影响，表明基因型-年龄相互作用可能起作用。
