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内皮型一氧化氮合酶基因外显子的深度靶向测序揭示了运动强度和种族依赖性与运动后低血压的关联。

Deep-targeted sequencing of endothelial nitric oxide synthase gene exons uncovers exercise intensity and ethnicity-dependent associations with post-exercise hypotension.

作者信息

Pescatello Linda S, Schifano Elizabeth D, Ash Garrett I, Panza Gregory A, Corso Lauren M L, Chen Ming-Hui, Deshpande Ved, Zaleski Amanda, Cilhoroz Burak, Farinatti Paulo, Taylor Beth A, O'Neill Rachel J, Thompson Paul D

机构信息

Department of Kinesiology, University of Connecticut, Storrs, Connecticut

Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut.

出版信息

Physiol Rep. 2017 Nov;5(22). doi: 10.14814/phy2.13510.

DOI:10.14814/phy2.13510
PMID:29180482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5704084/
Abstract

In previous studies, we found an endothelial nitric oxide synthase gene () variant rs2070744 associated with the ambulatory blood pressure (BP) response following bouts of moderate and vigorous intensity acute exercise, termed post-exercise hypotension (PEH). In a validation cohort, we sequenced exons for associations with PEH Obese (30.9 ± 3.6 kgm) African American ( = 14) [AF] and Caucasian ( = 9) adults 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects were attached to an ambulatory BP monitor for 19 h. We performed deep-targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini-Yekutieli multiple testing-corrected -values under time-adjusted linear models for 19 hourly BP measurements for each subject. After vigorous intensity over 19 h, among variants passing multiple testing thresholds, as the #MA increased in rs891512 ( = 6.4E-04), rs867225 ( = 6.5E-04), rs743507 ( = 2.6E-06), and rs41483644 ( = 2.4E-04), systolic (SBP) decreased from 17.5 to 33.7 mmHg; and in rs891512 ( = 9.7E-05), rs867225 ( = 2.6E-05), rs41483644 ( = 1.6E-03), rs3730009 ( = 2.6E-04), and rs77325852 ( = 5.6E-04), diastolic BP decreased from 11.1 mmHg to 20.3 mmHg among AF only. In contrast, after moderate intensity over 19 h in rs3918164, as the #MA increased, SBP increased by 16.6 mmHg ( = 2.4E-04) among AF only. variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. should be studied further for its effects on PEH in a large, ethnically diverse sample of adults with hypertension to confirm our findings.

摘要

在先前的研究中,我们发现内皮型一氧化氮合酶基因()变体rs2070744与中度和剧烈强度急性运动后的动态血压(BP)反应相关,这种反应被称为运动后低血压(PEH)。在一个验证队列中,我们对与PEH相关的外显子进行了测序。肥胖(30.9±3.6kg/m)的非裔美国(n = 14)[AF]和白种人(n = 9)成年人,年龄42.0±9.8岁,患有高血压(139.8±10.4/84.6±6.2mmHg),进行了三项随机实验:剧烈和中度强度的骑行以及对照实验。受试者佩戴动态血压监测仪19小时。我们使用Illumina TruSeq Custom Amplicon试剂盒进行深度靶向外显子测序。变体基因型被编码为次要等位基因数量(#MA),并根据Bonferonni或Benjamini - Yekutieli多重检验校正的P值,在每个受试者19小时血压测量的时间调整线性模型下,选择进行额外统计分析。在剧烈运动19小时后,在通过多重检验阈值的变体中,随着rs891512(P = 6.4E - 04)、rs867225(P = 6.5E - 04)、rs743507(P = 2.6E - 06)和rs41483644(P = 2.4E - 04)中#MA的增加,收缩压(SBP)从17.5mmHg降至33.7mmHg;在rs891512(P = 9.7E - 05)、rs867225(P = 2.6E - 05)、rs41483644(P = 1.6E - 03)、rs3730009(P = 2.6E - 04)和rs77325852(P = 5.6E - 04)中,仅在AF中舒张压从11.1mmHg降至20.3mmHg。相比之下,在rs3918164中进行19小时的中等强度运动后,随着#MA的增加,仅在AF中收缩压升高了16.6mmHg(P = 2.4E - 04)。仅在AF中,变体在剧烈运动后与PEH相关,但在中等强度运动后不相关。应在一个大型、种族多样化的高血压成年样本中进一步研究其对PEH的影响,以证实我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a268/5704084/90972468b699/PHY2-5-e13510-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a268/5704084/90972468b699/PHY2-5-e13510-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a268/5704084/90972468b699/PHY2-5-e13510-g001.jpg

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