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美国黑人的阿尔法球蛋白基因拷贝数与高血压风险。

Alpha globin gene copy number and hypertension risk among Black Americans.

机构信息

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.

Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, United States of America.

出版信息

PLoS One. 2022 Jul 14;17(7):e0271031. doi: 10.1371/journal.pone.0271031. eCollection 2022.

Abstract

BACKGROUND

Alpha globin is expressed in the endothelial cells of human resistance arteries where it binds to endothelial nitric oxide synthase and limits release of the vasodilator nitric oxide. Genomic deletion of the alpha globin gene (HBA) is common among Black Americans and could lead to increased endothelial nitric oxide signaling and reduced risk of hypertension.

METHODS

Community-dwelling US adults aged 45 years or older were enrolled and examined from 2003 to 2007, followed by telephone every 6 months, and reexamined from 2013 to 2016. At both visits, trained personnel performed standardized, in-home blood pressure measurements and pill bottle review. Prevalent hypertension was defined as systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg or anti-hypertensive medication use. Droplet digital PCR was used to determine HBA copy number. The associations of HBA copy number with prevalent hypertension, resistant hypertension, and incident hypertension were estimated using multivariable regression.

RESULTS

Among 9,684 Black participants, 7,439 (77%) had hypertension at baseline and 1,044 of those had treatment-resistant hypertension. 1,000 participants were not hypertensive at baseline and participated in a follow up visit; 517 (52%) developed hypertension over median 9.2 years follow-up. Increased HBA copy number was not associated with prevalent hypertension (PR = 1.00; 95%CI 0.98,1.02), resistant hypertension (PR = 0.95; 95%CI 0.86,1.05), or incident hypertension (RR = 0.96; 95%CI 0.86,1.07).

CONCLUSIONS

There were no associations between increased HBA copy number and risk of hypertension. These findings suggest that variation in alpha globin gene copy number does not modify the risk of hypertension among Black American adults.

摘要

背景

α珠蛋白在人类阻力血管的内皮细胞中表达,它与内皮型一氧化氮合酶结合,限制血管扩张剂一氧化氮的释放。α珠蛋白基因(HBA)的基因组缺失在非裔美国人中很常见,这可能导致内皮型一氧化氮信号增加和高血压风险降低。

方法

2003 年至 2007 年期间,招募了年龄在 45 岁或以上的美国社区居民并进行了检查,之后每 6 个月通过电话进行随访,并于 2013 年至 2016 年期间重新检查。在两次就诊时,经过培训的人员均在家中进行标准化血压测量和药瓶审查。高血压的定义为收缩压≥140mmHg 或舒张压≥90mmHg 或使用抗高血压药物。使用液滴数字 PCR 来确定 HBA 拷贝数。使用多变量回归估计 HBA 拷贝数与高血压、抗高血压药物抵抗性高血压和新发高血压的相关性。

结果

在 9684 名黑人参与者中,7439 名(77%)基线时患有高血压,其中 1044 名患有抗高血压药物抵抗性高血压。1000 名参与者基线时无高血压,并参加了随访;在中位 9.2 年的随访中,有 517 名参与者发生了高血压。HBA 拷贝数增加与高血压的患病率(PR = 1.00;95%CI 0.98,1.02)、抗高血压药物抵抗性高血压(PR = 0.95;95%CI 0.86,1.05)或新发高血压(RR = 0.96;95%CI 0.86,1.07)均无相关性。

结论

HBA 拷贝数增加与高血压风险之间没有关联。这些发现表明,α珠蛋白基因拷贝数的变化不会改变非裔美国成年人患高血压的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/835a/9282593/46b10fc7c0b0/pone.0271031.g001.jpg

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