摘要
G-protein coupled receptor kinase 4(GRK4)gene plays a core role in renal dopamine D1 receptor function for handing renal sodium excretion,the rs1801058 T variant has~50%frequency in the general East Asian population but lacks functional evidence for salt-sensitivity.In this prospective study,we identified rs1801058 genotypes by sequencing in hypertensives patients and analyzed the variant's effects on blood pressure response to acute salt loading in 150 newly diagnosed hypertension patients.Our data indicated that there were no statistically significant difference in blood pressure changes between the overall rs1801058 genotype groups.Carriers of the C allele showed a significant rise in heart rate change according to acute saline loading.Among patients age≤40year,T allele carriers showed higher changes in systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),and heart rate(HR)than C allele carriers when diuretic shrinkage.GRK4 single rs1801058 polymorphism cannot directly explain salt sensitivity in the Chinese hypertension patients.
肾脏多巴胺D1受体功能够促进肾脏尿钠排泄,而G蛋白偶联受体激酶4(GRK4)对肾脏多巴胺D1受体的功能起着重要作用,既往研究显示GRK4基因多态位点与高血压盐敏感性相关,其中rs1801058 T等位基因在东亚人群中约有50%的频率,但缺乏与盐敏感性相关的功能证据。本研究通过对高血压患者进行rs1801058基因测序,探索该位点多态性与患者急性盐负荷的血压反应的关联,从而进一步找到该位点与盐敏感性的关系。研究的数据表明,rs1801058基因型与盐负荷后的血压变化没有统计学显著差异,但携带C等位基因的患者表现出显著的心率增快;而利尿缩容后,在≤40岁的亚组患者中,T等位基因携带者的收缩压、舒张压、平均动脉压和心率的变化均高于C等位基因携带者。研究表明GRK4单个rs1801058多态性不能直接解释中国高血压患者的盐敏感性。
