Nierenberg Jovia L, Li Changwei, He Jiang, Gu Dongfeng, Chen Jichun, Lu Xiangfeng, Li Jianxin, Wu Xigui, Gu C Charles, Hixson James E, Rao Dabeeru C, Kelly Tanika N
From the Department of Epidemiology (J.L.N., C.L., J.H., T.N.K.) and Department of Medicine (J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA; Department of Epidemiology and Biostatistics, University of Georgia College of Public Health, Athens (C.L.); Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (D.G., J.C., X.L., J.L., X.W.); Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston (J.E.H.); and Division of Biostatistics, Washington University School of Medicine, St. Louis, MO (C.C.G., D.C.R.).
Hypertension. 2017 Dec;70(6):1106-1112. doi: 10.1161/HYPERTENSIONAHA.117.10108. Epub 2017 Oct 9.
We examined the association between genetic risk score (GRS) for blood pressure (BP), based on single nucleotide polymorphisms identified in previous BP genome-wide association study meta-analyses, and salt and potassium sensitivity of BP among participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). The GenSalt study was conducted among 1906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/d), 7-day high-sodium (307.8 mmol sodium/d), and 7-day high-sodium plus potassium (60 mmol potassium/d) intervention. BP was measured 9× at baseline and at the end of each intervention period using a random zero sphygmomanometer. Associations between systolic BP (SBP), diastolic BP, and mean arterial pressure GRS and respective SBP, diastolic BP, and mean arterial pressure responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, sex, field center, body mass index, and baseline BP. As expected, baseline SBP, diastolic BP, and mean arterial pressure significantly increased per quartile increase in GRS (=2.7×10, 9.8×10, and 6.4×10, respectively). In contrast, increasing GRS quartile conferred smaller SBP, diastolic BP, and mean arterial pressure responses to the low-sodium intervention (=1.4×10, 0.02, and 0.06, respectively) and smaller SBP responses to the high-sodium and potassium interventions (=0.10 and 0.05). In addition, overall findings were similar when examining GRS as a continuous measure. Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP. These data may provide novel implications on the relationship between BP responses to dietary sodium and potassium and hypertension.
我们基于既往血压全基因组关联研究荟萃分析中鉴定出的单核苷酸多态性,研究了血压(BP)的遗传风险评分(GRS)与盐敏感性和钾敏感性之间的关联,该研究在GenSalt研究(盐敏感性遗传流行病学网络)的参与者中进行。GenSalt研究纳入了1906名参与者,他们接受了为期7天的低钠(51.3 mmol钠/天)、7天高钠(307.8 mmol钠/天)和7天高钠加钾(60 mmol钾/天)干预。在基线以及每个干预期结束时,使用随机零位血压计测量9次血压。收缩压(SBP)、舒张压和平均动脉压GRS与各自的SBP、舒张压和平均动脉压对饮食干预的反应之间的关联,使用混合线性回归模型进行评估,该模型考虑了家族相关性,并对年龄、性别、研究中心、体重指数和基线血压进行了校正。正如预期的那样,GRS每增加一个四分位数,基线SBP、舒张压和平均动脉压显著升高(分别为=2.7×10、9.8×10和6.4×10)。相比之下,GRS四分位数增加时,对低钠干预的SBP、舒张压和平均动脉压反应较小(分别为=1.4×10、0.02和0.06),对高钠和钾干预的SBP反应较小(分别为0.10和0.05)。此外,将GRS作为连续变量进行检验时,总体结果相似。与我们最初的假设相反,我们发现血压GRS与血压的盐敏感性和钾敏感性之间存在负相关关系。这些数据可能为血压对饮食中钠和钾的反应与高血压之间的关系提供新的启示。