Bryant Tyler S, Duggal Priya, Yu Bing, Morrison Alanna C, Shafi Tariq, Ehret Georg, Franceschini Nora, Boerwinkle Eric, Coresh Josef, Tin Adrienne
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Int J Hypertens. 2019 Feb 18;2019:2137629. doi: 10.1155/2019/2137629. eCollection 2019.
[] encodes dimethylaniline monooxygenase [N-oxide-forming] 3, which breaks down nitrogen-containing compounds, and has been implicated in blood pressure regulation. Studies have reported conflicting results of the association of a common nonsynonymous variant, E158K (rs2266782), with hypertension. We examined the associations of E158K, along with rare and low frequency exonic variants (minor allele frequency [MAF]<5%) in with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP). We included 7,350 European Americans and 2,814 African Americans in the Atherosclerosis Risk in Communities (ARIC) study with exome sequencing of . The association of variants with SBP and DBP was tested using single variant and gene-based tests followed by the replication or interrogation of significant variants in ancestry-specific cohorts based on Bonferroni corrected thresholds. E158K had significant association with higher SBP in African Americans in ARIC (p=0.03), and two low frequency variants had significant association with higher SBP in African Americans (rs200985584, MAF 0.1%, p=0.0003) and European Americans (rs75904274, MAF 1.7%, p=0.006). These associations were not significant with additional samples: E158K in a meta-analysis of SBP of African ancestry (N=30,841, p=0.43) that included ARIC participants and the two low frequency variants in an independent ancestry-specific exome sequencing study of blood pressure (rs200985584, p=0.94; rs75904274, p=0.81). Our study does not support the association of E158K and low frequency variants in with blood pressure and demonstrates the importance of replication in genetic studies.
[]编码二甲基苯胺单加氧酶[N-氧化物形成]3，该酶可分解含氮化合物，并与血压调节有关。研究报告了一种常见的非同义变体E158K（rs2266782）与高血压关联的相互矛盾的结果。我们研究了E158K以及罕见和低频外显子变体（次要等位基因频率[MAF]<5%）与高血压、收缩压（SBP）和舒张压（DBP）的关联。我们纳入了社区动脉粥样硬化风险（ARIC）研究中的7350名欧洲裔美国人和2814名非洲裔美国人，并对其进行外显子组测序。使用单变体和基于基因的测试来检验变体与SBP和DBP的关联，随后根据Bonferroni校正阈值在特定祖先队列中对显著变体进行复制或验证。在ARIC研究中，E158K与非洲裔美国人较高的SBP有显著关联（p=0.03），两个低频变体与非洲裔美国人（rs200985584，MAF 0.1%，p=0.0003）和欧洲裔美国人（rs75904274，MAF 1.7%，p=0.006）较高的SBP有显著关联。在额外样本中这些关联并不显著：在一项包括ARIC参与者的非洲血统SBP荟萃分析（N=30841，p=0.43）中E158K的情况，以及在一项独立的特定祖先外显子组血压测序研究中两个低频变体（rs200985584，p=0.94；rs75904274，p=0.81）的情况。我们的研究不支持E158K和[相关基因]中的低频变体与血压的关联，并证明了基因研究中复制的重要性。
