He William J, Li Changwei, Rao Dabeeru C, Hixson James E, Huang Jianfeng, Cao Jie, Rice Treva K, Shimmin Lawrence C, Gu Dongfeng, Kelly Tanika N
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA; Isidore Newman School, New Orleans, Louisiana, USA;
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA;
Am J Hypertens. 2015 Nov;28(11):1310-5. doi: 10.1093/ajh/hpv033. Epub 2015 Mar 28.
The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure (BP) regulation. The current study uses single-marker and gene-based analyses to examine the association between RAAS genes and longitudinal BP phenotypes in a Han Chinese population.
A total of 1,768 participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current study. Twenty-seven BP measurements were taken using random-zero sphygmomanometers at baseline and 2 follow-up visits. Mixed-effect models were used to assess the additive associations of 106 single-nucleotide polymorphisms (SNPs) in 10 RAAS genes with longitudinal BP changes and hypertension incidence. Gene-based analyses were conducted using the truncated product method. Attempts were made to replicate significant findings among Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). False discovery rate procedures were used to adjust for multiple testing.
During an average of 7.2 years of follow-up, average systolic and diastolic BP increased, and 32.1% (512) of participants free from hypertension at baseline developed hypertension. NR3C2 SNPs rs7694064 and rs6856803 were significantly associated with longitudinal changes in systolic BP (P interaction = 6.9×10(-5) and 8.2×10(-4), respectively). Through gene-based analysis, NR3C2 was found to be significantly associated with longitudinal systolic BP change (P value of 1.00×10(-7)), even after removal of significant markers rs7694064 and rs6856803 from the analysis. The association between NR3C2 and longitudinal systolic BP change was replicated in Asian MESA participants (P value of 1.00×10(-4)).
These findings indicate that NR3C2 may play an important role in BP progression and development of hypertension.
肾素-血管紧张素-醛固酮系统（RAAS）在血压（BP）调节中起重要作用。本研究采用单标记和基于基因的分析方法，探讨RAAS基因与中国汉族人群纵向血压表型之间的关联。
本研究纳入了盐敏感性遗传流行病学网络（GenSalt）随访研究中的1768名参与者。在基线和2次随访时，使用随机零点血压计进行27次血压测量。采用混合效应模型评估10个RAAS基因中106个单核苷酸多态性（SNP）与纵向血压变化和高血压发病率的加性关联。使用截短乘积法进行基于基因的分析。尝试在动脉粥样硬化多族裔研究（MESA）的亚洲参与者中重复显著发现。采用错误发现率程序对多重检验进行校正。
在平均7.2年的随访期间，平均收缩压和舒张压升高，基线时无高血压的参与者中有32.1%（512人）发生了高血压。NR3C2基因的SNP rs7694064和rs6856803与收缩压的纵向变化显著相关（P交互作用分别为6.9×10⁻⁵和8.2×10⁻⁴）。通过基于基因的分析发现，即使在分析中去除显著标记rs7694064和rs6856803后，NR3C2仍与收缩压的纵向变化显著相关（P值为1.00×10⁻⁷）。NR3C2与收缩压纵向变化之间的关联在MESA研究的亚洲参与者中得到了重复（P值为1.00×10⁻⁴）。
这些发现表明NR3C2可能在血压进展和高血压发展中起重要作用。
