Seven lessons from two candidate genes in human essential hypertension - Angiotensinogen and epithelial sodium channel
Seven lessons from two candidate genes in human essential hypertension - Angiotensinogen and epithelial sodium channel
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DOI：
10.1161/01.hyp.33.6.1324
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发表时间：
1999-06-01
期刊：
影响因子：
8.3
通讯作者：
Jeunemaitre, X
中科院分区：
文献类型：
--
作者：
Corvol, P;Persu, A;Jeunemaitre, X
通过分析血管紧张素原（AGT）和上皮阿米洛利敏感性钠通道（ENaC）2个基因的作用，探讨了从候选基因角度理解原发性高血压遗传学的方法。从在人类和动物中进行的一系列研究来看，AGT基因似乎在人类血压变化中起着重要但适度的作用。β-和γ-ENaC亚单位的突变是导致Liddle综合征的原因，但3个ENaC亚单位在原发性高血压中的意义仍有疑问。从这些研究中可以学到一些经验，并应用于原发性高血压的其他候选基因：（1）许多连锁或关联研究的统计能力有限;（2）根据研究的人群，遗传结果可能差异很大;（3）需要更好的高血压人群表型;（4）分子变异与高血压之间的因果关系难以确定;（5）啮齿类动物遗传学研究对人类高血压分子遗传学的贡献必须重新审视;（6）大多数分子变异导致人群归因风险较低，或个体水平的个体效应较低;（7）根据患者基因型提出饮食建议和具体药物治疗还为时过早。
The candidate gene approach to understanding the genetics of human essential hypertension is discussed by analyzing the contribution of 2 genes, angiotensinogen (AGT) and epithelial amiloride-sensitive sodium channel (ENaC). From a large series of studies conducted in humans and animals, it appears that the AGT gene plays a significant but modest role in human blood pressure variance. Mutations of the beta- and gamma-ENaC subunits are responsible for Liddle's syndrome, but the implication of the 3 ENaC subunits in essential hypertension is still questionable. Several lessons can be learned from these studies and applied to other candidate genes in essential hypertension: (1) Many Linkage or association studies have a limited statistical power; (2) The genetic findings may vary greatly according to the populations studied; (3) There is a need for better phenotyping of the hypertensive population; (4) The causal relationship between molecular variants and hypertension is and will be difficult to establish firmly; (5) The contribution of genetic studied in rodents to the molecular genetics of human hypertension must be re-examined; (6) Most molecular variants lead to a low attributable risk in the population or a low individual effect at the individual level; and (7) It is too early to propose dietary recommendations and specific drug treatment according to patients' genotypes.