NEDD4L基因多态性与血压钠钾反应性的相关性分析  

Association of genetic variants in NEDD4L with blood pressure responses to dietary salt and potassium intake

作　　者：牛泽家馨 杜鸣飞 胡桂霖 张玺 王丹[1] 王兰 罗文婧 常鸣珂 邹婷 张晓玉 严瑜 褚超[1] 廖月圆 马琼[1] 王科科 贾昊 陈晨[1] 孙月 郭统帅[1] 张婕 高卫华[5] 满子悦 高可 牟建军[1] 汪洋[1,6] NIU Zejiaxin;DU Mingfei;HU Guilin;ZHANG Xi;WANG Dan;WANG Lan;LUO Wenjing;CHANG Mingke;ZOU Ting;ZHANG Xiaoyu;YAN Yu;CHU Chao;LIAO Yueyuan;MA Qiong;WANG Keke;JIA Hao;CHEN Chen;SUN Yue;GUO Tongshuai;ZHANG Jie;GAO Weihua;MAN Ziyue;GAO Ke;MU Jianjun;WANG Yang(Department of Cardiovascular Medicine,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;Department of Cardiology,Xi’an International Medical Center Hospital,Xi’an 710100;Department of Cardiology,Northwest Women’s and Children’s Hospital,Xi’an 710003;Department of Cardiology,Xi’an People’s Hospital,Xi’an 710004;Department of Cardiology,Xi’an No.1 Hospital,Xi’an 710002;Global Health Institute,Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院心内科,陕西西安710061 [2]西安国际医学中心医院心内科,陕西西安710100 [3]西北妇女儿童医院心内科,陕西西安710003 [4]西安市人民医院心内科,陕西西安710004 [5]西安市第一医院心内科,陕西西安710002 [6]西安交通大学全球健康研究院,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2023年第1期30-37,共8页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81600327,81870319,82070437);陕西省自然科学基金项目(No.2021JM-257,2021JM-588);西安交通大学第一附属医院院基金(No.2019QN-06、2021ZXY-14);西安交通大学第一附属医院临床研究项目(No.XJTU1AF-CRF-2019-004、XJTU1AF2021CRF-021)资助。

摘　　要：目的神经前体细胞表达发育下调的4样蛋白(NEDD4L)通过调节上皮钠通道蛋白在血压调节及钠稳态中发挥重要作用,本研究旨在探讨人群NEDD4L基因多态性与血压钠钾反应性的关系。方法2004年在陕西眉县招募的来自124个家系的514名受试者建立“盐敏感性高血压研究队列”,对受试者依次进行3 d基线调查、7 d低盐饮食、7 d高盐饮食、7 d高盐补钾饮食干预,测量不同干预期的受试者血压并采集外周血标本。采用MassARRAY检测平台对NEDD4L基因14个多态性位点分型检测并进行相关性分析。结果低盐期受试者的血压低于基线期血压,高盐期受试者血压显著高于低盐期,而补钾后血压较高盐期明显降低。NEDD4L基因的多态性位点SNPs rs74408486与低盐期收缩压、舒张压和平均动脉压反应性显著相关;而SNPs rs292449、rs2288775与高盐期脉压反应性显著相关;此外,rs563283、rs292449与高盐补钾期舒张压、平均动脉压及脉压反应性显著相关。结论NEDD4L基因多态性与血压的钠钾反应性密切相关,提示NEDD4L基因可能参与血压盐敏感性及钾反应性的发生发展。Objective 4-like protein with down-regulated expression and development in neural precursor cells(NEDD4L)plays an important role in blood pressure(BP)regulation and sodium homeostasis by regulating epithelial sodium channel protein.In this study,we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake.Methods In 2004,514 subjects from 124 families in Meixian County,Shaanxi Province,were recruited to establish a salt-sensitive hypertension study cohort.All the subjects received a 3-day baseline survey,a7-day low-salt diet,a7-day high-salt diet,and finally a7-day high-salt and potassium supplementation.Their BP was measured and peripheral blood samples were collected at different intervention periods.The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform.Results BP decreased on a low-salt diet,and significantly increased on a high-salt diet,and decreased again after potassium supplementation.NEDD4L SNPs rs74408486 were significantly associated with systolic BP,diastolic BP and mean arterial pressure responses to the low-salt diet.SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet.In addition,SNPs rs563283 and rs292449 were significantly associated with diastolic BP,mean arterial pressure,and pulse pressure responses to high-salt and potassium supplementation diet.Conclusion NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake,suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

关 键 词：NEDD4L 基因多态性 血压 盐敏感性 钾 

分 类 号：R541.3[医药卫生—心血管疾病]