Association of hypertension with T594M mutation in β subunit of epithelial sodium channels in black people resident in London
Association of hypertension with T594M mutation in β subunit of epithelial sodium channels in black people resident in London
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DOI：
10.1016/s0140-6736(97)07306-6
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发表时间：
1998-05-09
期刊：
影响因子：
168.9
通讯作者：
MacGregor, GA
中科院分区：
文献类型：
--
作者：
Baker, EH;Dong, YB;MacGregor, GA
背景利德尔综合征是一种罕见的遗传性高血压，其中上皮钠通道突变导致肾钠重吸收增加。黑人原发性高血压患者也表现出钠潴留的临床特征，因此我们筛选了黑人T594 M突变，这是最常见的钠通道突变。在一项病例对照研究中，对206名高血压（平均年龄48.0 [SD 11.8]岁，男性：女性80：126）和142名血压正常（48.7 [7.4]岁; 61：81）的黑人（居住在英国伦敦）进行T594 M筛查。通过PCR扩增来自基因组DNA的上皮钠通道β亚基的最后一个外显子的一部分。通过PCR产物的单链构象多态性分析检测T594 M变异体，并通过DNA测序确认。206例高血压患者中有17例（8.3%）携带T594 M变异，而142例正常血压患者中有3例（2.1%）携带T594 M变异（OR =4.17 [95%CI 1.12-18.25]，p = 0.029）。高比例的T594 M变异的参与者是女性（17名高血压参与者中的15名和所有3名血压正常的参与者），而女性在筛选的个体中所占比例较低（61.2%高血压，57.7%血压正常）。然而，在调整性别和体重指数后，T594 M变异体与高血压之间的相关性仍然存在（Mantel-Haenszel OR=5.52 [1.40-30.61]，p = 0.012）。13名携带T594 M变异的高血压患者的血浆肾素活性（中位数=0.19 ng mL（-1）h（-1））显著低于39名未接受治疗的高血压患者（中位数=0.45 ng mL（-1）h（-1），p=0.009）。在伦敦黑人中，T594 M钠通道β亚基突变在高血压患者中的发生率高于非高血压患者。T594 M变异可能会增加钠通道活性，并通过增加肾小管钠重吸收来升高受影响人群的血压。这些发现表明，T594 M突变可能是迄今为止黑人原发性高血压最常见的次要原因。
Background. Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation.Methods. In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive (48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel beta subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing.Findings. 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normotensive partcipants possessed the T594M variant (odds ratio [OR]=4.17 [95% CI 1.12-18.25], p = 0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2% hypertensive, 57.7% normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR=5.52 [1.40-30.61], p = 0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median=0.19 ng mL(-1) h(-1)) than in 39 untreated hypertensive individuals without the variant (median=0.45 ng mL(-1) h(-1), p=0.009).Interpretation. Among black London people the T594M sodium-channel beta subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.