Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults
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 signalling in arterial endothelial cells via interactions with nitric oxide synthase; however, its ro...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-12-01
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| Series: | BMJ Open Respiratory Research |
| Online Access: | https://bmjopenrespres.bmj.com/content/10/1/e001714.full |
| _version_ | 1797370952711929856 |
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| author | Michael P Fay Loretta G Que A Parker Ruhl Jarrett M Jackson Carlos J Carhuas Jessica G Niño de Rivera J Brice Weinberg Hans C Ackerman |
| author_facet | Michael P Fay Loretta G Que A Parker Ruhl Jarrett M Jackson Carlos J Carhuas Jessica G Niño de Rivera J Brice Weinberg Hans C Ackerman |
| author_sort | Michael P Fay |
| collection | DOAJ |
| description | 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 signalling in arterial endothelial cells via interactions with nitric oxide synthase; however, its role in regulating the release of NO from respiratory epithelium is less well understood. We hypothesised 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 to 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 immunoglobulin-E 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 (25th, 75th) 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 to 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 to 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. |
| first_indexed | 2024-03-08T18:12:48Z |
| format | Article |
| id | doaj.art-8c05ecbd115f487b933fa161e0acf5e1 |
| institution | Directory Open Access Journal |
| issn | 2052-4439 |
| language | English |
| last_indexed | 2024-03-08T18:12:48Z |
| publishDate | 2023-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Respiratory Research |
| spelling | doaj.art-8c05ecbd115f487b933fa161e0acf5e12024-01-01T03:20:08ZengBMJ Publishing GroupBMJ Open Respiratory Research2052-44392023-12-0110110.1136/bmjresp-2023-001714Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adultsMichael P Fay0Loretta G Que1A Parker Ruhl2Jarrett M Jackson3Carlos J Carhuas4Jessica G Niño de Rivera5J Brice Weinberg6Hans C Ackerman7Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USADepartment of Medicine and Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine and Durham VA Medical Centers, Durham, North Carolina, USALaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USALaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USALaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USALaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USADepartment of Medicine and Division of Hematology, Duke University School of Medicine and Durham VA Medical Centers, Durham, North Carolina, USALaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USAIntroduction 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 signalling in arterial endothelial cells via interactions with nitric oxide synthase; however, its role in regulating the release of NO from respiratory epithelium is less well understood. We hypothesised 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 to 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 immunoglobulin-E 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 (25th, 75th) 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 to 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 to 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.https://bmjopenrespres.bmj.com/content/10/1/e001714.full |
| spellingShingle | Michael P Fay Loretta G Que A Parker Ruhl Jarrett M Jackson Carlos J Carhuas Jessica G Niño de Rivera J Brice Weinberg Hans C Ackerman Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults BMJ Open Respiratory Research |
| title | Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults |
| title_full | Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults |
| title_fullStr | Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults |
| title_full_unstemmed | Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults |
| title_short | Association of alpha globin gene copy number with exhaled nitric oxide in a cross-sectional study of healthy Black adults |
| title_sort | association of alpha globin gene copy number with exhaled nitric oxide in a cross sectional study of healthy black adults |
| url | https://bmjopenrespres.bmj.com/content/10/1/e001714.full |
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