High alpha-globin gene copy count correlates with CKD among Black Americans
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An increase in alpha-globin gene copy number was associated with a greater prevalence of chronic kidney disease and incidence of end-stage kidney disease in Black Americans, according to published data.
“[Alpha]-globin is expressed in endothelial cells of resistance arteries, where it limits endothelial nitric oxide signaling and enhances alpha-adrenergic–mediated vasoconstriction. [Alpha]-globin gene (HBA) copy number is variable in people of African descent and other populations worldwide,” A. Parker Ruhl, MD, MHS, from the Laboratory of Malaria and Vector Research at the Institutes of Health in Maryland, and colleagues wrote. “In light of the newly recognized function of alpha-globin as a restrictor of endothelial nitric oxide signaling, we hypothesized that alpha-globin gene deletions would be associated with protection against prevalent CKD, incident reduced eGFR and incident ESKD among Black Americans.”
In the national, longitudinal cohort Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, 30,329 community dwelling participants from the U.S. (41% were Black) were enrolled from 2003 to 2007.
Participants measured baseline variables using standardized computer-assisted telephone interviews, self-administered questionnaires and in-home physical examinations. At the in-home examinations, trained personnel evaluated height, weight and blood pressure in addition to collecting blood and urine specimens.
Droplet digital PCR measured HBA copy number, and modified Poisson multivariable regression determined the prevalence ratio of CKD and risk of incident reduced eGFR. Cox proportional hazards multivariable regression measured the hazard ratio of incident ESKD.
The primary outcome was considered CKD prevalence.
Among the 9,918 Black patients who met inclusion and exclusion criteria, 393 patients (4%) had two HBA copies, 2,744 (28%) had three HBA copies, 6,668 (67%) had four copies, 101 (1%) had five HBA copies and two (<1%) patients had six HBA copy numbers.
Adjusted analyses revealed that a one-copy increase in HBA correlated with 14% greater prevalence of CKD and 32% higher hazards of incident ESKD. HBA copy was not associated with incident eGFR.
The limitations of this study include the lack of an independent replication cohort.
“In conclusion, we report that higher HBA copy number was independently associated with greater CKD prevalence and ESKD incidence after accounting for known clinical, demographic and genetic risk factors in this national longitudinal study of Black Americans,” Ruhl and colleagues wrote. “The high frequency of the HBA gene deletion found in Black Americans may act to reduce the overall burden of kidney disease in this population.”
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