Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 May;24(2):e111-e115.
doi: 10.1093/pch/pxy106. Epub 2018 Aug 6.

The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation

Graham Sinclair  1 , Sorcha Collins  2 , Laura Arbour  2 , Hilary Vallance  1
Affiliations

The p.P479L variant in CPT1A is associated with infectious disease in a BC First Nation

Graham Sinclair et al. Paediatr Child Health. 2019 May.

Abstract

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.

Keywords: Carnitine palmitoyltransferase; Fatty acid oxidation; First Nation; Indigenous; Infection.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bartlett K, Eaton S. Mitochondrial beta-oxidation. Eur J Biochem 2004;271(3):462–9. - PubMed
    1. Gessner BD, Gillingham MB, Johnson MA, et al. . Prevalence and distribution of the c.1436c→t sequence variant of carnitine palmitoyltransferase 1A among Alaska native infants. J Pediatr 2011;158(1):124–9. - PubMed
    1. Collins SA, Sinclair G, McIntosh S, et al. . Carnitine palmitoyltransferase 1A (CPT1A) P479L prevalence in live newborns in Yukon, northwest territories, and Nunavut. Mol Genet Metab 2010;101(2–3):200–4. - PubMed
    1. Sinclair GB, Collins S, Popescu O, McFadden D, Arbour L, Vallance HD. Carnitine palmitoyltransferase I and sudden unexpected infant death in British Columbia First Nations. Pediatrics 2012;130(5):e1162–9. - PubMed
    1. Rajakumar C, Ban MR, Cao H, Young TK, Bjerregaard P, Hegele RA. Carnitine palmitoyltransferase IA polymorphism p479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I. J Lipid Res 2009;50(6):1223–8. - PMC - PubMed