Pankow J S, Rose K M, Oberman A, Hunt S C, Atwood L D, Djoussé L, Province M A, Rao D C
Department of Epidemiology, University of North Carolina, Chapel Hill, USA. jim
Hypertension. 2000 Oct;36(4):471-6. doi: 10.1161/01.hyp.36.4.471.
We conducted a genome-wide scan for quantitative trait loci influencing the systolic blood pressure, diastolic blood pressure, and pulse responses to a postural challenge in 498 white sibling-pairs from the Hypertension Genetic Epidemiology Network, a multicenter study of the genetic susceptibility to hypertension. All participants were hypertensive (systolic blood pressure >/=140 mm Hg, diastolic blood pressure >/=90 mm Hg, or on antihypertensive medications) with diagnosis before age 60. Blood pressure and pulse were measured by an oscillometric method after a 5-minute rest in a supine position and again immediately on standing. The genome scan included a total of 387 autosomal short-tandem-repeat polymorphisms typed by the National Heart, Lung, and Blood Institute Mammalian Genotyping Service at Marshfield. We used multipoint variance-components linkage analysis to identify possible quantitative trait loci influencing postural change phenotypes after adjusting for sex, age, and use of antihypertensive medications. There was suggestive evidence for linkage on chromosome 18q for the postural systolic blood pressure response (maximum logarithm of the odds score=2.6 at 80 centiMorgans). We also observed a maximum logarithm of the odds score of 1.9 for the systolic blood pressure response and 1.7 for the diastolic blood pressure response on chromosome 6p. The marker that demonstrated the strongest evidence for linkage for the systolic blood pressure response (D18S858) lies within 20 centiMorgans of a marker previously linked to rare familial orthostatic hypotensive syndrome. Our findings indicate that there may be 1 or more genes on chromosome 18q that regulate systolic blood pressure during the physiological recovery period after a postural stressor.
我们在高血压遗传流行病学网络（一项关于高血压遗传易感性的多中心研究）的498对白人同胞对中，进行了全基因组扫描，以寻找影响收缩压、舒张压以及对体位改变反应时脉搏的数量性状基因座。所有参与者均为高血压患者（收缩压≥140 mmHg，舒张压≥90 mmHg，或正在服用抗高血压药物），且在60岁之前被诊断出患有高血压。在仰卧位休息5分钟后，通过示波法测量血压和脉搏，站立后立即再次测量。基因组扫描共包括387个常染色体短串联重复多态性，由位于马什菲尔德的美国国立心肺血液研究所哺乳动物基因分型服务中心进行分型。我们使用多点方差成分连锁分析，在调整了性别、年龄和抗高血压药物使用情况后，确定影响体位改变表型的可能数量性状基因座。有提示性证据表明，18号染色体长臂上存在与体位性收缩压反应相关的连锁（在80厘摩处，优势对数得分最大值为2.6）。我们还观察到，6号染色体短臂上收缩压反应的优势对数得分最大值为1.9，舒张压反应的优势对数得分最大值为1.7。在收缩压反应方面显示出最强连锁证据的标记（D18S858），位于一个先前与罕见家族性直立性低血压综合征相关的标记的20厘摩范围内。我们的研究结果表明，18号染色体长臂上可能存在1个或更多基因，在体位应激源后的生理恢复期调节收缩压。
