Work

Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults

Year: 2023

Type: article

Abstract: ABSTRACT Introduction The genetic determinants of fractional exhalation of nitric oxide (FeNO), a marker of lung inflammation, are understudied in Black individuals. Alpha globin ( HBA ) restricts nitric oxide signaling in arterial endothelial cells via interactions with nitric oxide synthase (NOS); however, its role in regulating the release of NO from respiratory epithelium is less well understood. We hypothesized that an HBA gene deletion, common among Black individuals, would be associated with higher FeNO. Methods Healthy Black adults were enrolled at four study sites in North Carolina from 2005-2008. FeNO was measured in triplicate using a nitric oxide analyzer. The −3.7 kb HBA gene deletion was genotyped using droplet digital PCR on genomic DNA. The association of FeNO with HBA copy number was evaluated using multivariable linear regression employing a linear effect of HBA copy number and adjusting for age, sex, and serum IgE levels. Post-hoc analysis employing a recessive mode of inheritance was performed. Results 895 individuals were in enrolled in the study and 720 consented for future genetic research; 643 had complete data and were included in this analysis. Median (25 th , 75 th ) FeNO was 20 (13, 31) ppb. HBA genotypes were: 30 (4.7%) -a/-a, 197 (30.6%) -a/aa, 405 (63%) aa/aa, and 8 (1.2%) aa/aaa. Subjects were 35% male with median age 20 (19, 22) years. Multivariable linear regression analysis revealed no association between FeNO and HBA copy number (β = −0.005 [95% CI: −0.042, 0.033], p=0.81). In the post-hoc sensitivity analysis, homozygosity for the HBA gene deletion was associated with higher FeNO (β = 0.107 [95% CI 0.003, 0.212]; p = 0.045) Conclusion We found no association between HBA copy number and FeNO using a prespecified additive genetic model. However, a post hoc recessive genetic model found FeNO to be higher among subjects homozygous for the HBA deletion. KEY MESSAGES What is already known on this topic – The alpha subunit of hemoglobin restricts the release of nitric oxide from vascular endothelial cells, but alpha globin’s role in restricting exhaled nitric oxide is less well understood. What this study adds – We examined the association between fractional exhaled nitric oxide and deletion of the alpha globin gene, a frequent genetic polymorphism among people with African or Asian ancestry. We found that healthy Black individuals who were homozygous for the alpha globin gene deletion had higher fractional exhaled nitric oxide, consistent with alpha globin’s role as a nitric oxide restrictor. How this study might affect research, practice or policy – An alpha globin gene deletion, commonly found among Black individuals, may increase fractional exhaled nitric oxide. Whether this changes the normal range of fractional exhaled nitric oxide for Black individuals or impacts the risk of developing asthma requires further study.

Source: BMJ Open Respiratory Research

DOI: 10.1136/bmjresp-2023-001714