Hypertension Center.
State Key Laboratory of Cardiovascular Diseases.
J Hypertens. 2018 Mar;36(3):502-509. doi: 10.1097/HJH.0000000000001556.
The study aimed to analyze genes involved in Mendelian forms of low-renin hypertension in Chinese early-onset hypertensive patients.
A panel of nine genes, namely SCNN1B, SCNN1G, WNK1, WNK4, KLHL3, CUL3, nuclear receptor subfamily 3, group C (NR3C)1, NR3C2, and HSD11B2 were screened by targeted resequencing in 260 Chinese early-onset hypertensive patients. Additionally, exon 13 of both SCNN1B and SCNN1G was sequenced in an independent cohort of 506 Chinese early-onset hypertensive patients.
About 81 nonrare and 41 rare variants were, respectively, detected in 221 (85.0%) and 39 (15.0%) patients from the cohort of 260. Of the total 766 patients, those with rare variants in exon 13 of either SCNN1B or SCNN1G had a significantly earlier onset of hypertension (24.7 ± 7.5 vs. 29.0 ± 7.7 years, P = 0.015) and lower serum potassium (3.57 ± 0.59 vs. 3.96 ± 0.41 mmol/l, P = 0.007) than those without rare variants. However, other identified rare variants had no effects on clinical expression. Seven patients (0.91%) were diagnosed with Liddle's syndrome, and the Liddle's syndrome prevalence was 1.72% among the 407 patients with hypertension diagnosed before the age of 30. Genetic screening of the probands' relatives identified 10 additional Liddle's syndrome patients. Treatment of Liddle's syndrome patients with amiloride resulted in normalization of both blood pressure and serum potassium.
Liddle's syndrome appears to be the most common low-renin Mendelian hypertension in young Chinese hypertensive patients. Sequencing exon 13 of both SCNN1B and SCNN1G is highly advisable in patients with early-onset and low-renin hypertension.
本研究旨在分析中国早发性高血压患者中涉及低肾素性高血压孟德尔形式的基因。
通过靶向重测序，在 260 例中国早发性高血压患者中筛选了 9 个基因，即 SCNN1B、SCNN1G、WNK1、WNK4、KLHL3、CUL3、核受体亚家族 3 组 C（NR3C）1、NR3C2 和 HSD11B2。此外，在 506 例中国早发性高血压患者的独立队列中，对 SCNN1B 和 SCNN1G 的外显子 13 进行了测序。
在 260 例患者的队列中，分别在 221 例（85.0%）和 39 例（15.0%）患者中检测到 81 个非稀有和 41 个稀有变异。在总共 766 例患者中，SCNN1B 或 SCNN1G 的外显子 13 中存在稀有变异的患者，其高血压发病年龄更早（24.7±7.5 岁比 29.0±7.7 岁，P=0.015），血清钾水平更低（3.57±0.59mmol/L 比 3.96±0.41mmol/L，P=0.007）。然而，其他鉴定的稀有变异对临床表达没有影响。7 例（0.91%）患者被诊断为利德尔综合征，在 30 岁前被诊断为高血压的 407 例患者中，利德尔综合征的患病率为 1.72%。对先证者亲属进行遗传筛查，又发现了 10 例利德尔综合征患者。用氨苯蝶啶治疗利德尔综合征患者，使血压和血清钾均恢复正常。
利德尔综合征似乎是中国年轻高血压患者中最常见的低肾素性孟德尔高血压。在早发性、低肾素性高血压患者中，强烈建议对 SCNN1B 和 SCNN1G 的外显子 13 进行测序。
