原发性醛固酮增多症患者KCNJ5基因变异对其心脏的损害作用

摘要
图/表
参考文献(23)
相关文章 (0)

全文: PDF (352 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的分析原发性醛固酮增多症患者内向整流钾通道J亚家族成员5（KCNJ5）基因变异情况及临床资料，探讨在原发性醛固酮增多症中KCNJ5基因不同突变位点患者的心脏损害情况。方法收集2011年1月~2015年12月在新疆维吾尔自治区人民医院高血压中心诊治的10例单侧肾上腺皮质增生（UAH）、18例醛固酮腺瘤（APA）患者，记录其一般临床资料、生化指标、KCNJ5基因型，并行超声心动图检查。比较分析患者的不同突变位点、临床资料、生化指标、超声心动图检查结果。结果 28例患者中G151突变患者7例，L168突变患者5例，S209突变患者16例，G151患者收缩压及醛固酮肾素活性比值（ARR）较L168、S209突变患者高，其血钾低于L168、S209突变患者，差异均有统计学意义（P ＜ 0.05）。G151突变患者左室舒张期内径、左室后壁厚度、左室重量（LVM）高于其他两种突变类型患者，其射血分数（EF）低于L168、S209突变患者，但三者间差异无统计学意义（P ＞ 0.05）。在APA患者中，G151突变患者左室舒张期内径、LVM大于其他两种突变类型患者，且与L168突变患者比较差异有统计学意义（P ＜ 0.05）。结论原发性醛固酮增多症患者中不同KCNJ5基因变异对靶器官的损害程度可能存在差异，G151突变患者心脏损害等情况较L168、S209突变严重。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	胡君丽洪静吴婷李娟骆秦王国亮王梦卉李南方

关键词 ：原发性醛固酮增多症, 醛固酮腺瘤, 单侧肾上腺皮质增生, KCNJ5基因, 不同突变位点

Abstract：Objective To analyze the genetic variation and clinical data of the inward rectifier potassium channel J subfamily member 5 (KCNJ5) in patients with primary aldosteronism, and to investigate the cardiac damage in patients with different KCNJ5 gene mutations in primary aldosteronism. Methods From January 2011 to December 2015, 10 patients with unilateral adrenal cortical hyperplasia (UAH) and 18 patients with aldosterone-producing adenoma (APA) were collected from the Hypertension Center of the People′s Hospital of Xinjiang Uygur Autonomous Region. The general clinical data, biochemical parameters, KCNJ5 genotype were recorded, and echocardiography was performed. Results Among the 128 patients, 7 patients had G151 mutation, 5 patients with L168 mutation, and 16 patients with S209 mutation, and the systolic blood pressure and aldosterone renin activity ratio (ARR) of G151 mutation were higher than those of L168 and S209 mutation, and their blood potassium levels were lower than those of L168 and S209 mutation, and the differences were statistical significant (P < 0.05). The left ventricular diastolic diameter, left ventricular posterior wall thickness and left ventricular mass (LVM) of patients with G151 mutation were higher than those of patients with other two mutation types, and their ejection fraction (EF) was lower than those of patients with L168 and S209 mutation, but there was no significant difference among the three mutations (P > 0.05). In APA patients, the left ventricular diastolic diameter and LVM of G151 mutation patients were higher than those of the other two mutation types, and there were significant difference compared with L168 mutation patients (P < 0.05). Conclusion The degree of damage of different KCNJ5 gene mutations in target aldosteronism patients may be different. The heart damage of patients with G151 mutation is more serious than that of L168 and S209.

Key words： Primary aldosteronism Aldosterone-producing adenoma Unilateral adrenal cortical hyperplasia KCNJ5 gene Different mutations

基金资助:国家自然科学基金资助项目（81460078）。

通讯作者: 李南方（1958.7-），女，教授，主任医师；研究方向：高血压临床与基础。

引用本文:

胡君丽洪静吴婷李娟骆秦王国亮王梦卉李南方. 原发性醛固酮增多症患者KCNJ5基因变异对其心脏的损害作用[J]. 中国医药导报, 2019, 16(8): 63-67.
HU Junli HONG Jing WU Ting LI Juan LUO Qin WANG Guoliang WANG Menghui LI Nanfang. Heart damage caused by KCNJ5 gene mutation in patients with primary aldosteronism. 中国医药导报, 2019, 16(8): 63-67.

链接本文:

http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2019/V16/I8/63

[1] Kline GA，Aph P，Leung AA，et al. Primary aldosteronism：a common cause of resistant hypertension [J]. CMAJ，2017， 189（22）：E773-E778.
[2] Monticone S，Burrello J，Tizzani D，et al. Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice [J] Am Coll Cardiol，2017， 69（14）：1811-1820.
[3] Monticone S，D′Ascenzo F，Moretti C，et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension：a systematic review and meta-analysis [J]. Lancet Diabetes Endocrinol，2017， 6（1）：41-50.
[4] Mulatero P，Monticone S，Bertello C，et al. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism [J]. J Clin Endocrinol Metab，2013，98（12）：4826-4833.
[5] Savard S，Amar L，Plouin PF，et al. Cardiovascular complications associated with primary aldosteronism：a controlled cross-sectional study [J]. Hypertension，2013，62（2）：331-336.
[6] Murata M，Kitamura T，Tamada D，et al. Plasma aldosterone level within the normal range is less associated with cardiovascular and cerebrovascular risk in primary aldosteronism [J]. Hypertens，2017，35（5）：1079-1085.
[7] Ladurner R，Sommerey S，Buechner S，et al. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism [J]. Eur J Clin Invest 2017，47（5）：372-377.
[8] Kim IY，Park IS，Kim MJ，et al. Change in kidney function after unilateral adrenalectomy in patients with primary aldosteronism：identification of risk factors for decreased kidney function [J]. Int Urol Nephrol，2018，50（10）：1887-1895.
[9] Monticone S，Hattangady NG，Nishimoto K，et al. Effect of KCNJ5 mutations on gene expression in aldosterone-producing adenomas and adrenoeortieal cells [J]. Clin Endoerinol Metab，2012，97（8）：E1567-E1572.
[10] Tauber P，Penton D，Stindl J，et al. Pharmacology and pathophysiology of mutated KCNJ5 found in adrenal aldosterone producing adenomas [J]. Endocrinology，2014， 155（4）：1353-1362.
[11] Choi M，Scholl UI，Yue P，et al. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension [J]. Science，2011，331（6018）：768-772.
[12] 张晶晶，李南方，胡燕荣，等.单侧肾上腺增生性原发性醛固酮增多症KCNJ5基因序列的检测[J].中华医学遗传学杂志，2015，32（1）：21-25.
[13] Kitamoto T，Suematsu S，Matsuzawa Y，et al. Comparison of cardiovascular complications in patients with and without KCNJ5 gene mutations harboring aldosterone-producing adenomas [J]. J Atheroscler Thromb，2015，22（2）：191-200.
[14] Kitamoto T，Omura M，Suematsu S，et al. KCNJ5 mutation as a predictor for resolution of hypertension after surgical treatment of aldosterone-producing adenoma [J]. J Hypertens，2018，36（3）：619-627.
[15] Funder JW，Carey RM，Mantero F，et al. The Management of Primary Aldosteronism：Case Detection，Diagnosis，and Treatment：An Endocrine Society Clinical Practice Guideline [J]. J Clin Endocrinol Metab，2016，101（5）：1889-1916.
[16] Mansia G，De Backer G，Dominiczak A，et a1. 2003 European society of hypertension European society of cardiology guidelines for the management of arterial hypertension，Guidelines committee [J]. J Hypertens，2003，21（6）：1011-1053.
[17] Chang CH，Hu YH，Tsai YC，et al. Arterial stiffness and blood pressure improvement in aldosterone-producing adenoma harboring KCNJ5 mutations after adrenalectomy [J]. Oncotarget，2017，8（18）：29 984-29 995.
[18] 李南方，马轩，王红梅，等.原发性醛固酮增多症患者蛋白尿情况分析[J].中华高血压杂志，2013，21（3）：249-252.
[19] Ohno Y，Sone M，Inagaki N，et al. Prevalence of Cardiovascular Disease and Its Risk Factors in Primary Aldosteronism：A Multicenter Study in Japan [J]. Hypertension，2018，71（3）：530-537.
[20] Okamura T，Nakajima Y，Katano-Toki A，et al. Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations [J]. Endocr J，2017，64（1）：39-47.
[21] Zhang L，Lee JK，John SA，et al. Mechanosensitivity of GIRK Channels Is Mediated by Protein Kinase C-dependent Channel-Phosphatidylinositol 4,5-Bisphosphate Interaction [J]. J Biol Chem，2004，279（8）：7037-7047.
[22] Treiber F，Rosker C，Keren-Raifman T，et al. Molecular basis of the facilitation of the heterooligomeric GIRK1/GIRK4 complex by cAMP dependent proteinkinase [J]. Biochim Biophys Acta，2013，1828（4）：1214-1221.
[23] Cheng CJ，Sung CC，Wu ST，et al. Novel KCNJ5 mutations in sporadic aldosterone-producing adenoma reduce Kir3.4 membrane abundance [J]. J Clin Endocrinol Metab， 2015，100（1）：155-163.