Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans,Journal of the American Society of Nephrology

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Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans
Journal of the American Society of Nephrology ( IF 13.6 ) Pub Date : 2022-01-01 , DOI: 10.1681/asn.2021050653
A Parker Ruhl _{1,

2} , Neal Jeffries ₃ , Yu Yang ₄ , Rakhi P Naik ₅ , Amit Patki ₆ , Lydia H Pecker ₅ , Bryan T Mott ₇ , Neil A Zakai _{8,

9} , Cheryl A Winkler ₁₀ , Jeffrey B Kopp ₁₁ , Leslie A Lange ₁₂ , Marguerite R Irvin ₁₃ , Orlando M Gutierrez _{13,

14} , Mary Cushman _{8,

9} , Hans C Ackerman ₁

Affiliation

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, Rockville, Maryland.
Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama.
University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.
Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont.
Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont.
Basic Research Program, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado, Denver, Colorado.
Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama.
Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.

Background

α-Globin is expressed in endothelial cells of resistance arteries, where it limits endothelial nitric oxide signaling and enhances α-adrenergic–mediated vasoconstriction. α-Globin gene (HBA) copy number is variable in people of African descent and other populations worldwide. Given the protective effect of nitric oxide in the kidney, we hypothesized that HBA copy number would be associated with kidney disease risk.

Methods

Community-dwelling Black Americans aged ≥45 years old were enrolled in a national longitudinal cohort from 2003 through 2007. HBA copy number was measured using droplet digital PCR. The prevalence ratio (PR) of CKD and the relative risk (RR) of incident reduced eGFR were calculated using modified Poisson multivariable regression. The hazard ratio (HR) of incident ESKD was calculated using Cox proportional hazards multivariable regression.

Results

Among 9908 participants, HBA copy number varied from 2 to 6. In analyses adjusted for demographic, clinical, and genetic risk factors, a one-copy increase in HBA was associated with 14% greater prevalence of CKD (PR, 1.14; 95% CI, 1.07 to 1.21; P<0.0001). While HBA copy number was not associated with incident reduced eGFR (RR, 1.06; 95% CI, 0.94 to 1.19; P=0.38), the hazard of incident ESKD was 32% higher for each additional copy of HBA (HR, 1.32; 95% CI, 1.09 to 1.61; P=0.005).

Conclusions

Increasing HBA copy number was associated with a greater prevalence of CKD and incidence of ESKD in a national longitudinal cohort of Black Americans.

中文翻译：

α 珠蛋白基因拷贝数与美国黑人中流行的慢性肾脏病和终末期肾脏病事件有关

背景

α-珠蛋白在阻力动脉的内皮细胞中表达，在那里它限制内皮一氧化氮信号并增强α-肾上腺素能介导的血管收缩。α-珠蛋白基因 ( HBA)拷贝数在非洲人后裔和世界其他人群中是可变的。鉴于一氧化氮对肾脏的保护作用，我们假设HBA拷贝数与肾脏疾病风险相关。

方法

从 2003 年到 2007 年，年龄≥45 岁的社区居住美国黑人被纳入全国纵向队列。HBA拷贝数使用液滴数字 PCR 测量。使用改良的泊松多变量回归计算 CKD 的患病率 (PR) 和 eGFR 降低事件的相对风险 (RR)。使用 Cox 比例风险多变量回归计算事件 ESKD 的风险比 (HR)。

结果

在 9908 名参与者中，HBA拷贝数从 2 到 6 不等。在针对人口统计学、临床和遗传风险因素进行调整的分析中，HBA 拷贝数增加14 % 与 CKD 患病率增加 14% 相关（PR，1.14；95% CI ，1.07 至 1.21；P <0.0001）。虽然HBA拷贝数与事件降低的 eGFR 无关（RR，1.06；95% CI，0.94 至 1.19；P = 0.38），但每增加一个HBA拷贝，发生 ESKD 的风险就会增加 32% （HR，1.32；95 % CI，1.09 至 1.61；P =0.005）。

结论

在美国黑人的全国纵向队列中，增加HBA拷贝数与 CKD 患病率和 ESKD 发病率增加相关。

更新日期：2021-12-31

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