Supplementary Material for: Downregulation of Arntl mRNA Expression in Women with Hypertension: A Case-Control Study

Background: Previous studies have reported that disturbance of endogenous circadian rhythms enhances the chance of hypertension and suggested that circadian clock genes could have a crucial function in the onset of the disease. This case-control study was aimed to investigate the association of the mRNA expression of aryl hydrocarbon receptor nuclear translocator like (Arntl), clock circadian regulator (Clock), and period circadian regulators 1 and 2 (Per1 and Per2) with hypertension and blood pressure levels. Methods: A total of 172 subjects were recruited in this study, including 86 hypertension and 86 nonhypertension controls. The mRNA expression levels in peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction. The differences in Arntl, Clock, Per1, and Per2 mRNA expression were compared between the 2 groups, and the relationship between mRNA expression and cardiometabolic risk profiles was also assessed. Results: We found that the mRNA expression of Arntl was downregulated in the hypertension cases compared with controls in women (1.10 [0.66, 1.71] vs. 1.30 [0.99, 2.06], p = 0.031). There was a significant negative correlation between the Arntl mRNA expression and SBP (r = −0.301, p = 0.004) and DBP (r = −0.222, p = 0.034) in women. In men, a negative correlation between the Per1 mRNA expression and SBP (r = −0.247, p = 0.026) was found. Conclusions: The Arntl mRNA expression may play an important role in progression of hypertension in women.

背景：既往研究表明，内源性昼夜节律紊乱会增加高血压发病风险，且提示昼夜节律钟基因在该疾病的发生中发挥关键作用。本病例对照研究旨在探讨芳香烃受体核转运蛋白样基因（aryl hydrocarbon receptor nuclear translocator like, Arntl）、时钟昼夜节律调节因子（clock circadian regulator, Clock）以及周期昼夜节律调节因子1和2（period circadian regulators 1 and 2, Per1和Per2）的mRNA表达水平与高血压及血压水平的关联。方法：本研究共纳入172名研究对象，其中高血压病例组、非高血压对照组各86例。采用实时定量聚合酶链反应检测外周血单个核细胞中的mRNA表达水平。对比两组间Arntl、Clock、Per1及Per2的mRNA表达差异，并评估mRNA表达与心血管代谢风险谱的相关性。结果：女性亚组中，高血压病例组的Arntl mRNA表达水平较对照组显著下调（1.10 [0.66, 1.71] vs. 1.30 [0.99, 2.06]，p=0.031）。女性亚组中，Arntl mRNA表达水平与收缩压（systolic blood pressure, SBP）（r=-0.301，p=0.004）及舒张压（diastolic blood pressure, DBP）（r=-0.222，p=0.034）均呈显著负相关。男性亚组中，Per1 mRNA表达水平与SBP呈显著负相关（r=-0.247，p=0.026）。结论：Arntl mRNA表达可能在女性高血压的发生发展中发挥重要作用。