Zafarmand Mohammad Hadi, van der Schouw Yvonne T, Grobbee Diederick E, de Leeuw Peter W, Bots Michiel L
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Str 6.131, 3584 CX Utrecht, Utrecht, The Netherlands.
Hypertension. 2008 Jun;51(6):1665-70. doi: 10.1161/HYPERTENSIONAHA.108.112458. Epub 2008 May 5.
The Gly460Trp variant of the alpha-adducin gene has been associated with renal sodium retention and salt-sensitive hypertension. Independent of blood pressure, salt sensitivity has been related to cerebrovascular events. We studied the risk of stroke, coronary heart disease (CHD), and myocardial infarction (MI) associated with the alpha-adducin variant and examined the extent to which this risk is modified by the presence of hypertension. We performed a case-cohort study in a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model with an estimation procedure adapted for case-cohort designs to study the relation of the polymorphism and CHD (n=210), MI (n=71), any stroke (n=74), and ischemic stroke (n=49). Subjects with the Gly460Trp variant had a 2.8 times higher risk of stroke (95% confidence intervals [CI] 1.3 to 5.8) under the dominant genetic model, which did not attenuate after adjustment. The same pattern was found under per-allele comparison. Risk of ischemic stroke in the variant allele carriers was 3.9 times higher than in subjects with the common genotype (95% CI 1.7 to 8.6) using dominant inheritance model. The same patterns were found under per-allele comparison. CHD and MI were not related to the variant. The risk of ischemic stroke was more pronounced among women with systolic hypertension (10.9; 95% CI 3.6 to 31.5). The findings in this prospective study in a population based cohort of Dutch women strongly suggest that presence of the alpha-adducin Gly460Trp polymorphism increases the risk of stroke. This risk is particularly elevated in the presence of systolic hypertension.
α-内收蛋白基因的Gly460Trp变异与肾钠潴留及盐敏感性高血压有关。独立于血压之外，盐敏感性与脑血管事件相关。我们研究了与α-内收蛋白变异相关的中风、冠心病（CHD）和心肌梗死（MI）风险，并考察了高血压的存在对该风险的影响程度。我们在一个由15236名初始健康的荷兰女性组成的前瞻性队列中进行了一项病例队列研究。我们应用了一种适用于病例队列设计的估计程序的Cox比例风险模型，以研究该多态性与CHD（n = 210）、MI（n = 71）、任何中风（n = 74）和缺血性中风（n = 49）之间的关系。在显性遗传模型下，携带Gly460Trp变异的受试者中风风险高2.8倍（95%置信区间[CI] 1.3至5.8），调整后该风险并未减弱。在每个等位基因比较中也发现了相同的模式。使用显性遗传模型，变异等位基因携带者的缺血性中风风险比具有常见基因型的受试者高3.9倍（95% CI 1.7至8.6）。在每个等位基因比较中也发现了相同的模式。CHD和MI与该变异无关。缺血性中风风险在收缩期高血压女性中更为显著（10.9；95% CI 3.6至31.5）。在这个基于荷兰女性人群队列的前瞻性研究中的发现强烈表明，α-内收蛋白Gly460Trp多态性的存在增加了中风风险。在存在收缩期高血压的情况下，这种风险尤其升高。
