The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation
BACKGROUND: The hepatic carnitine palmitoyltransferase I (CPT1A) p.P479L variant is common in Aboriginal populations across coastal British Columbia, Alaska, the Canadian North, and Greenland. While the high frequency of this variant suggests positive selection, other studies have shown an associati...
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ftpubmed:oai:pubmedcentral.nih.gov:6462176 2023-05-15T16:16:51+02:00 The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation Sinclair, Graham Collins, Sorcha Arbour, Laura Vallance, Hilary 2019-05 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462176/ http://www.ncbi.nlm.nih.gov/pubmed/30996616 https://doi.org/10.1093/pch/pxy106 en eng Oxford University Press http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462176/ http://www.ncbi.nlm.nih.gov/pubmed/30996616 http://dx.doi.org/10.1093/pch/pxy106 © The Author(s) 2018. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Online Only Original Articles Text 2019 ftpubmed https://doi.org/10.1093/pch/pxy106 2020-04-19T00:14:51Z BACKGROUND: The hepatic carnitine palmitoyltransferase I (CPT1A) p.P479L variant is common in Aboriginal populations across coastal British Columbia, Alaska, the Canadian North, and Greenland. While the high frequency of this variant suggests positive selection, other studies have shown an association with sudden unexpected death in infancy and infection. We utilized administrative health data to evaluate hospitalizations for a single year cohort of children of First Nations descent genotyped for the variant and, matched for location of birth. Seven years of data were reviewed for 150 children split evenly between CPT1A genotypes (homozyous, heterozygous, and noncarrier of the p.P479L variant). RESULTS: Children homozygous for the p.P479L allele had a higher rate of hospital admissions at 2.6 per individual as compared to noncarriers at 0.86. Heterozygous children also showed a significant increase at 1.9 per person. Length of stay per admission was increased for both p.P479L homozygotes and heterozygotes. The odds ratio (OR) for at least one hospitalization for any reason was increased for p.P479L homozygotes relative to noncarriers (OR=10.2, confidence interval [CI] 3.5 to 30.0) as were admissions for dental caries (OR=3.4, CI 1.5 to 7.8), acute lower respiratory tract infections (OR=6.0, CI 1.6 to 22.4), and otitis media (OR=13.5, CI 1.7 to 109.4). CONCLUSIONS: The CPT1A p.P479L variant is associated with an increased rate of hospitalization for those homozygous, primarily for infectious disease causes. Heterozygotes also showed a small but significant increase in hospitalization rates suggesting some dosage effect. Functional studies will be required to identify the underlying pathological mechanism. Text First Nations Greenland Alaska PubMed Central (PMC) Greenland Paediatrics & Child Health 24 2 e111 e115 |
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Online Only Original Articles Sinclair, Graham Collins, Sorcha Arbour, Laura Vallance, Hilary The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation |
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Online Only Original Articles |
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BACKGROUND: The hepatic carnitine palmitoyltransferase I (CPT1A) p.P479L variant is common in Aboriginal populations across coastal British Columbia, Alaska, the Canadian North, and Greenland. While the high frequency of this variant suggests positive selection, other studies have shown an association with sudden unexpected death in infancy and infection. We utilized administrative health data to evaluate hospitalizations for a single year cohort of children of First Nations descent genotyped for the variant and, matched for location of birth. Seven years of data were reviewed for 150 children split evenly between CPT1A genotypes (homozyous, heterozygous, and noncarrier of the p.P479L variant). RESULTS: Children homozygous for the p.P479L allele had a higher rate of hospital admissions at 2.6 per individual as compared to noncarriers at 0.86. Heterozygous children also showed a significant increase at 1.9 per person. Length of stay per admission was increased for both p.P479L homozygotes and heterozygotes. The odds ratio (OR) for at least one hospitalization for any reason was increased for p.P479L homozygotes relative to noncarriers (OR=10.2, confidence interval [CI] 3.5 to 30.0) as were admissions for dental caries (OR=3.4, CI 1.5 to 7.8), acute lower respiratory tract infections (OR=6.0, CI 1.6 to 22.4), and otitis media (OR=13.5, CI 1.7 to 109.4). CONCLUSIONS: The CPT1A p.P479L variant is associated with an increased rate of hospitalization for those homozygous, primarily for infectious disease causes. Heterozygotes also showed a small but significant increase in hospitalization rates suggesting some dosage effect. Functional studies will be required to identify the underlying pathological mechanism. |
format |
Text |
author |
Sinclair, Graham Collins, Sorcha Arbour, Laura Vallance, Hilary |
author_facet |
Sinclair, Graham Collins, Sorcha Arbour, Laura Vallance, Hilary |
author_sort |
Sinclair, Graham |
title |
The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation |
title_short |
The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation |
title_full |
The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation |
title_fullStr |
The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation |
title_full_unstemmed |
The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation |
title_sort |
p.p479l variant in cpt1a is associated with infectious disease in a bc first nation |
publisher |
Oxford University Press |
publishDate |
2019 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462176/ http://www.ncbi.nlm.nih.gov/pubmed/30996616 https://doi.org/10.1093/pch/pxy106 |
geographic |
Greenland |
geographic_facet |
Greenland |
genre |
First Nations Greenland Alaska |
genre_facet |
First Nations Greenland Alaska |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462176/ http://www.ncbi.nlm.nih.gov/pubmed/30996616 http://dx.doi.org/10.1093/pch/pxy106 |
op_rights |
© The Author(s) 2018. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) |
op_doi |
https://doi.org/10.1093/pch/pxy106 |
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Paediatrics & Child Health |
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24 |
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2 |
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e111 |
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e115 |
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1766002696624537600 |