Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut
Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, C...
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ftpubmed:oai:pubmedcentral.nih.gov:8290072 2023-05-15T15:11:47+02:00 Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut Collins, Sorcha A. Edmunds, Sharon Akearok, Gwen Healey Thompson, J. Robert Erickson, Anders C. Hildes-Ripstein, Elske Miners, Amber Somerville, Martin Goldfarb, David M. Rockman-Greenberg, Cheryl Arbour, Laura 2021-07-06 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290072/ https://doi.org/10.3389/fped.2021.678553 en eng Frontiers Media S.A. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290072/ http://dx.doi.org/10.3389/fped.2021.678553 Copyright © 2021 Collins, Edmunds, Akearok, Thompson, Erickson, Hildes-Ripstein, Miners, Somerville, Goldfarb, Rockman-Greenberg and Arbour. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. CC-BY Front Pediatr Pediatrics Text 2021 ftpubmed https://doi.org/10.3389/fped.2021.678553 2021-07-25T00:43:35Z Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, Canada, and Greenland. CPT1A is a fatty acid oxidation enzyme expressed in the liver, immunocytes and other tissues, and is needed to use fats for energy during fasting. Previous association of the variant with early childhood infectious illness and infant death has been challenged because of sample size and limited adjustment for confounders. We evaluated whether the p.P479L variant is associated with infectious illness in Inuit children of Nunavut, Canada. Methods: We conducted a retrospective clinical chart review of 2,225 Inuit children (0–5 years) for infectious illness (including otitis media, gastroenteritis, and hospital admission for LRTI), prenatal, perinatal, and socioeconomic indicators, subsequently linking to CPT1A genotype. Multivariable logistic regression adjusted for birth characteristics, breastfeeding, maternal smoking, food insecurity, and socioeconomic indicators. Results: Overall, 27% of children were hospitalized for LRTI, 86% had otitis media and 50% had gastroenteritis. The p.P479L allele frequency was 0.82. In multivariable analysis, p.P479L homozygosity was associated with LRTI admission (aOR:2.88 95%CI:1.46–5.64), otitis media (aOR:1.83, 95%CI:1.05–3.21), and gastroenteritis (aOR:1.74, 95%CI:1.09–2.77), compared to non-carriers. Conclusion: Children homozygous for the p.P479L variant were more likely to experience infectious illness than non-carriers, including hospitalization for respiratory tract infections. Given the role of CPT1A in immunocytes, our findings indicate that more study is needed to determine if there is a role of the variant in immune response. Continued Inuit involvement is essential when considering next steps. Text Arctic Greenland inuit Nunavut Alaska PubMed Central (PMC) Arctic Canada Greenland Nunavut Frontiers in Pediatrics 9 |
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English |
topic |
Pediatrics |
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Pediatrics Collins, Sorcha A. Edmunds, Sharon Akearok, Gwen Healey Thompson, J. Robert Erickson, Anders C. Hildes-Ripstein, Elske Miners, Amber Somerville, Martin Goldfarb, David M. Rockman-Greenberg, Cheryl Arbour, Laura Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut |
topic_facet |
Pediatrics |
description |
Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, Canada, and Greenland. CPT1A is a fatty acid oxidation enzyme expressed in the liver, immunocytes and other tissues, and is needed to use fats for energy during fasting. Previous association of the variant with early childhood infectious illness and infant death has been challenged because of sample size and limited adjustment for confounders. We evaluated whether the p.P479L variant is associated with infectious illness in Inuit children of Nunavut, Canada. Methods: We conducted a retrospective clinical chart review of 2,225 Inuit children (0–5 years) for infectious illness (including otitis media, gastroenteritis, and hospital admission for LRTI), prenatal, perinatal, and socioeconomic indicators, subsequently linking to CPT1A genotype. Multivariable logistic regression adjusted for birth characteristics, breastfeeding, maternal smoking, food insecurity, and socioeconomic indicators. Results: Overall, 27% of children were hospitalized for LRTI, 86% had otitis media and 50% had gastroenteritis. The p.P479L allele frequency was 0.82. In multivariable analysis, p.P479L homozygosity was associated with LRTI admission (aOR:2.88 95%CI:1.46–5.64), otitis media (aOR:1.83, 95%CI:1.05–3.21), and gastroenteritis (aOR:1.74, 95%CI:1.09–2.77), compared to non-carriers. Conclusion: Children homozygous for the p.P479L variant were more likely to experience infectious illness than non-carriers, including hospitalization for respiratory tract infections. Given the role of CPT1A in immunocytes, our findings indicate that more study is needed to determine if there is a role of the variant in immune response. Continued Inuit involvement is essential when considering next steps. |
format |
Text |
author |
Collins, Sorcha A. Edmunds, Sharon Akearok, Gwen Healey Thompson, J. Robert Erickson, Anders C. Hildes-Ripstein, Elske Miners, Amber Somerville, Martin Goldfarb, David M. Rockman-Greenberg, Cheryl Arbour, Laura |
author_facet |
Collins, Sorcha A. Edmunds, Sharon Akearok, Gwen Healey Thompson, J. Robert Erickson, Anders C. Hildes-Ripstein, Elske Miners, Amber Somerville, Martin Goldfarb, David M. Rockman-Greenberg, Cheryl Arbour, Laura |
author_sort |
Collins, Sorcha A. |
title |
Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut |
title_short |
Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut |
title_full |
Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut |
title_fullStr |
Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut |
title_full_unstemmed |
Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut |
title_sort |
association of the cpt1a p.p479l metabolic gene variant with childhood respiratory and other infectious illness in nunavut |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290072/ https://doi.org/10.3389/fped.2021.678553 |
geographic |
Arctic Canada Greenland Nunavut |
geographic_facet |
Arctic Canada Greenland Nunavut |
genre |
Arctic Greenland inuit Nunavut Alaska |
genre_facet |
Arctic Greenland inuit Nunavut Alaska |
op_source |
Front Pediatr |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290072/ http://dx.doi.org/10.3389/fped.2021.678553 |
op_rights |
Copyright © 2021 Collins, Edmunds, Akearok, Thompson, Erickson, Hildes-Ripstein, Miners, Somerville, Goldfarb, Rockman-Greenberg and Arbour. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.3389/fped.2021.678553 |
container_title |
Frontiers in Pediatrics |
container_volume |
9 |
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