Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion.
Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion.
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DOI：
10.1371/journal.pgen.0010082
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发表时间：
2005-12
期刊：
影响因子：
4.5
通讯作者：
Chakravarti A
中科院分区：
文献类型：
--
作者：
Young JH;Chang YP;Kim JD;Chretien JP;Klag MJ;Levine MA;Ruff CB;Wang NY;Chakravarti A
高血压是中风、心脏病和肾衰竭的主要原因。血压变化的遗传基础在很大程度上是未知的，但可能涉及影响肾脏盐分处理和动脉血管紧张性的基因。在这里，我们认为高血压的易感性是祖传的，高血压的不同易感性是由于在非洲以外的扩张期间不同地暴露于选择压力。最重要的选择压力是气候，它产生了热适应的纬向倾斜性，因此，高血压易感性。与这一假设一致的是，我们发现，纬度、温度和降雨量等生态变量可以解释全球范围内热适应的差异，这是由参与血压调节的五个基因中的七个功能等位基因定义的。热适应的纬度跃变在全球范围内是一致的，在短串联重复标记、控制单核苷酸多态或五个基因内无功能的单核苷酸多态方面，纬度跃变在很大程度上是无法匹配的。此外，我们还发现，纬度和其中一个等位基因GNB3(G蛋白β3亚基)825T是全球血压变化的主要原因。这些结果表明，目前的高血压流行是由于现代时期暴露与祖先的易感性相互作用所致。然而，现代人群对这些新暴露的易感性不同，因此来自炎热环境的人比来自寒冷环境的人更容易患高血压。这种不同的易感性可能是由于我们对气候的适应历史所致。高血压是中风、心脏病和肾衰竭的主要原因。高血压是由于年龄较大、高盐摄入量、肥胖和遗传易感性等因素造成的。导致高血压易感性增加的基因变异在很大程度上是未知的，但可能包括那些增加盐分滞留和血管紧张性的基因变异。在这里，作者指出，世界各地的人群对高血压的易感性不同，来自炎热潮湿环境的人群比来自寒冷环境的人群更容易患高血压。这种不同的易感性可能是由于50,000到100,000年前人类走出非洲时的选择所致。此外，作者还表明，纬度和增加高血压易感性的遗传变异之一，是全球血压变化的主要原因。因此，目前的高血压流行是由于祖先的易感性与现代时期的新危险因素相互作用，如高盐摄入量和肥胖。然而，不同人群对这些风险因素的易感性不同。这种不同的易感性是由于我们对气候的适应历史所致。
Hypertension is a leading cause of stroke, heart disease, and kidney failure. The genetic basis of blood pressure variation is largely unknown but is likely to involve genes that influence renal salt handling and arterial vessel tone. Here we argue that susceptibility to hypertension is ancestral and that differential susceptibility to hypertension is due to differential exposure to selection pressures during the out-of-Africa expansion. The most important selection pressure was climate, which produced a latitudinal cline in heat adaptation and, therefore, hypertension susceptibility. Consistent with this hypothesis, we show that ecological variables, such as latitude, temperature, and rainfall, explain worldwide variation in heat adaptation as defined by seven functional alleles in five genes involved in blood pressure regulation. The latitudinal cline in heat adaptation is consistent worldwide and is largely unmatched by latitudinal clines in short tandem repeat markers, control single nucleotide polymorphisms, or non-functional single nucleotide polymorphisms within the five genes. In addition, we show that latitude and one of these alleles, GNB3 (G protein β3 subunit) 825T, account for a major portion of worldwide variation in blood pressure. These results suggest that the current epidemic of hypertension is due to exposures of the modern period interacting with ancestral susceptibility. Modern populations differ in susceptibility to these new exposures, however, such that those from hot environments are more susceptible to hypertension than populations from cold environments. This differential susceptibility is likely due to our history of adaptation to climate. High blood pressure, or hypertension, is a leading cause of stroke, heart disease, and kidney failure. Hypertension is due to factors such as older age, high salt intake, obesity, and genetic susceptibility. The genetic variants responsible for increased susceptibility to hypertension are largely unknown but are likely to include those that increase salt retention and blood vessel tone. Here the authors show that populations around the world differ in susceptibility to hypertension such that populations from hot, wet environments are more susceptible to hypertension than populations from cold environments. This differential susceptibility is likely due to selection during the human out-of-Africa expansion 50,000 to 100,000 y ago. Furthermore, the authors show that latitude and one of the genetic variants that increase susceptibility to hypertension account for a major portion of worldwide variation in blood pressure. Therefore, the current epidemic of hypertension is due to ancestral susceptibility interacting with the new risk factors of the modern period, such as high salt intake and obesity. Populations differ in susceptibility to these risk factors, however. This differential susceptibility is due to our history of adaptation to climate.
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影响因子：
8.3
作者：
Baker, EH;Ireson, NJ;MacGregor, GA
通讯作者：
MacGregor, GA
影响因子：
8.3
作者：
Iwai, N;Baba, S;Ogata, J
通讯作者：
Ogata, J
影响因子：
158.5
作者：
Dishy, V;Sofowora, GG;Wood, AJJ
通讯作者：
Wood, AJJ
DOI：
10.1111/j.1440-1681.2005.04217.x
发表时间：
2005-05-01
影响因子：
2.9
作者：
Kumar, A;Li, Y;Jain, S
通讯作者：
Jain, S
影响因子：
8.3
作者：
BURT, VL;WHELTON, P;LABARTHE, D
通讯作者：
LABARTHE, D