Harvard Medical School, Institute for Aging Research/Hebrew SeniorLife/Beth Israel Deaconess Medical Center, Division of Gerontology, Boston, MA 02130, USA.
Stroke. 2010 Apr;41(4):635-40. doi: 10.1161/STROKEAHA.109.572669. Epub 2010 Feb 25.
Our objective was to investigate the associations between polymorphisms in representative genes of the renin angiotensin system with measures of cerebral blood flow regulation in older adults.
Participants in this analysis were white subjects (n=335) in the MOBILIZE Boston study (Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston), an observational study of community-dwelling elders who underwent transcranial Doppler while sitting and standing and during hypercapnea and hypocapnea. Autoregulation phenotype was the change in cerebrovascular resistance from sit to stand. Vasoreactivity phenotype was the slope of the change in cerebrovascular conductance versus change in end-tidal CO2. A total of 33 tagged single nucleotide polymorphisms were selected in the angiotensinogen gene, the angiotensin converting enzyme gene, and the angiotensin receptor gene. Regression analyses adjusted for age, gender, body mass index, mean arterial blood pressure, stroke, and use of antihypertensives were conducted for each single nucleotide polymorphism and outcome. Bonferroni corrections were used to adjust P values for multiple testing.
In the angiotensinogen gene, only the rs699 single nucleotide polymorphism was associated with vasoreactivity after Bonferroni correction (P=0.00028). Homozygous carriers of the CC genotype of this single nucleotide polymorphism had lower vasoreactivity compared with the CT or TT genotypes. There were no significant associations with autoregulation measures. None of the single nucleotide polymorphisms in the other genes were associated with our phenotypes.
This analysis suggests that the angiotensinogen gene may be involved in vasoreactivity independent of blood pressure. Larger studies are needed to confirm the role of this gene in cerebrovascular health and aging.
我们的目的是研究肾素-血管紧张素系统代表性基因的多态性与老年人脑血流调节测量值之间的相关性。
本分析的参与者是波士顿 Mobilize 研究（波士顿老年人的平衡、独立生活、智力和活力维持）中的白种人受试者（n=335），这是一项针对社区居住老年人的观察性研究，他们在坐位和站位、高碳酸血症和低碳酸血症期间接受了经颅多普勒检查。自动调节表型是从坐位到站立位时脑血管阻力的变化。血管反应性表型是脑血管导纳对呼气末二氧化碳变化的斜率。在血管紧张素原基因、血管紧张素转换酶基因和血管紧张素受体基因中总共选择了 33 个标记单核苷酸多态性。对每个单核苷酸多态性和结果进行了回归分析，调整了年龄、性别、体重指数、平均动脉血压、中风和使用降压药。采用 Bonferroni 校正对多重检验的 P 值进行了调整。
在血管紧张素原基因中，只有 rs699 单核苷酸多态性在经过 Bonferroni 校正后与血管反应性相关（P=0.00028）。该单核苷酸多态性的 CC 基因型纯合子的血管反应性低于 CT 或 TT 基因型。与自动调节测量值无显著相关性。其他基因中的单核苷酸多态性均与我们的表型无关。
本分析表明血管紧张素原基因可能与血压无关的血管反应性有关。需要更大的研究来确认该基因在脑血管健康和衰老中的作用。
