居住在伦敦的黑人中高血压与上皮钠通道β亚基T594M突变的关联。

Association of hypertension with T594M mutation in beta subunit of epithelial sodium channels in black people resident in London.

作者信息

Baker E H, Dong Y B, Sagnella G A, Rothwell M, Onipinla A K, Markandu N D, Cappuccio F P, Cook D G, Persu A, Corvol P, Jeunemaitre X, Carter N D, MacGregor G A

机构信息

Department of Pharmacology, St George's Hospital Medical School, London, UK.

出版信息

Lancet. 1998 May 9;351(9113):1388-92. doi: 10.1016/s0140-6736(97)07306-6.

DOI:10.1016/s0140-6736(97)07306-6

PMID:9593408

Abstract

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 participants 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.

摘要

背景

利德尔综合征是一种罕见的遗传性高血压，上皮钠通道突变导致肾脏钠重吸收增加。黑人原发性高血压也表现出钠潴留的临床特征，因此我们对黑人进行了T594M突变筛查，这是最常见的钠通道突变。

方法

在一项病例对照研究中，对居住在英国伦敦的206名高血压患者（平均年龄48.0[标准差11.8]岁，男∶女为80∶126）和142名血压正常者（48.7[7.4]岁；61∶81）进行T594M筛查。通过聚合酶链反应（PCR）扩增基因组DNA中上皮钠通道β亚基最后一个外显子的部分片段。通过PCR产物的单链构象多态性分析检测T594M变异，并通过DNA测序进行确认。

结果

206名高血压参与者中有17名（8.3%）携带T594M变异，而142名血压正常参与者中有3名（2.1%）携带该变异（比值比[OR]=4.17[95%可信区间1.12 - 18.25]，p = 0.029）。携带T594M变异的参与者中女性比例较高（17名高血压参与者中有15名，3名血压正常参与者均为女性），而在接受筛查的个体中女性所占比例较低（高血压患者中为61.2%，血压正常者中为57.7%）。然而，在对性别和体重指数进行校正后，T594M变异与高血压之间的关联仍然存在（Mantel-Haenszel OR = 5.52[1.40 - 30.61]，p = 0.012）。13名携带T594M变异的高血压参与者的血浆肾素活性（中位数 = 0.19 ng·mL⁻¹·h⁻¹）显著低于39名未携带该变异的未治疗高血压个体（中位数 = 0.45 ng·mL⁻¹·h⁻¹，p = 0.009）。