尿调节素基因多态性与血压钠钾反应性的相关性分析  

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

作　　者：吴燕[1] 杜鸣飞 张玺 王兰 胡桂霖 牛泽家馨 邹婷 张晓玉 褚超[1] 廖月圆 马琼[1] 王丹[1] 王科科 贾昊 陈晨[1] 严瑜 孙月 郭统帅[1] 张婕 高卫华[5] 满子悦 高可 罗文婧 牟建军[1] 汪洋[1,6] WU Yan;DU Mingfei;ZHANG Xi;WANG Lan;HU Guilin;NIU Zejiaxin;ZOU Ting;ZHANG Xiaoyu;CHU Chao;LIAO Yueyuan;MA Qiong;WANG Dan;WANG Keke;JIA Hao;CHEN Chen;YAN Yu;SUN Yue;GUO Tongshuai;ZHANG Jie;GAO Weihua;MAN Ziyue;GAO Ke;LUO Wenjing;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38-45,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)资助;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)。

摘　　要：目的通过对本课题组早期建立的“盐敏感性高血压研究队列”进行钠钾饮食干预,旨在探讨人群尿调节素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”,对其中的333名非父母者进行3 d正常饮食—7 d低盐饮食—7 d高盐饮食—7 d高盐补钾饮食。采用MassARRAY检测平台对尿调节素基因13个多态性位点进行分型检测。结果低盐饮食可使受试者的血压下降,高盐饮食可使血压明显升高,而补钾可拮抗高盐饮食所致的血压上升。尿调节素基因的多态性位点rs7193058、rs4997081与高盐期舒张压和平均动脉压反应性显著相关。此外,rs77875418、rs79245268、rs4293393、rs6497476、rs4997081、rs13333226、rs12917707与高盐补钾期收缩压、舒张压和平均动脉压反应性显著相关。结论尿调节素基因多态性与血压的钠钾反应性紧密相关,提示尿调节素基因可能参与血压的钠、钾敏感性的形成。Objective Based on our previously established salt-sensitive hypertension cohort,we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP)responses to dietary interventions of sodium and potassium intake.Methods In 2004,514 subjects from 124 families in Mei County,Shaanxi Province were recruited to establish the salt-sensitive hypertension study cohort.Among them,333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days,low-salt diet for 7 days,then a high-salt diet for 7days and a high-salt diet with potassium supplementation for another 7 days.Thirteen single nucleotide polymorphisms(SNPs)in the uromodulin gene were genotyped on the MassARRAY platform.Results BP levels decreased from the baseline to low-salt diet,increased from low-salt to high-salt diet,and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention.SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP)and mean arterial pressure(MAP)responses to high-salt diet.In addition,SNPs rs77875418,rs79245268,rs4293393,rs6497476,rs4997081,rs13333226,and rs12917707 were significantly associated with systolic BP(SBP),DBP,and MAP responses to high-salt diet with potassium supplementation.Conclusion Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation,suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

关 键 词：尿调节素 基因多态性 血压 盐 钾 

分 类 号：R541.3[医药卫生—心血管疾病]