Carnitine palmitoyltransferase I and sudden unexpected infant death in British Columbia First Nations
Graham B Sinclair1, Sorcha Collins, Oana Popescu
1Departmens of aPathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia. gsinclair@cw.bc.ca
Insights
The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in coastal First Nations in British Columbia. Homozygosity for this variant is linked to higher rates of sudden unexpected infant death in these communities.
Area of Science:
- Genetics and Genomics
- Population Health
- Biochemistry
Background:
- Infant mortality rates are disproportionately high among First Nations in British Columbia.
- The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is prevalent in certain Indigenous populations and may contribute to infant mortality.
- Understanding the genetic and environmental factors influencing infant health in First Nations communities is crucial.
Purpose of the Study:
- To evaluate the efficacy of acylcarnitine profiling in identifying the CPT1A p.P479L variant.
- To determine the frequency and distribution of the CPT1A p.P479L variant within British Columbia's First Nations population.
- To investigate the association between the CPT1A p.P479L variant and sudden unexpected infant deaths in this demographic.
Main Methods:
- Genotyping of the CPT1A p.P479L variant in newborn screening cards from BC First Nations infants (2004) and infants who experienced sudden unexpected death (1999-2009).
- Linking genetic data with existing acylcarnitine profile data.
- Statistical analysis including odds ratio calculation to assess the association with infant mortality.
Main Results:
- The CPT1A p.P479L variant is frequent in BC First Nations, with higher homozygosity rates (up to 25%) observed in coastal regions.
- A significant overrepresentation of p.P479L homozygotes was found in unexpected infant deaths from these coastal areas (OR=3.92).
- Acylcarnitine profiling demonstrated high accuracy (94% sensitivity and specificity) for identifying p.P479L homozygotes.
Conclusions:
- The CPT1A p.P479L variant is common in specific coastal BC First Nations communities.
- Infant homozygosity for the CPT1A p.P479L variant is associated with an increased risk of unexpected death during infancy.
- The variant's high prevalence suggests a potential selective advantage, indicating context-dependent health impacts.
Objective:
Infant mortality in British Columbia (BC) First Nations remains elevated relative to other residents. The p.P479L (c.1436C>T) variant of carnitine palmitoyltransferase 1 (CPT1A) is frequent in some aboriginal populations and may be associated with increased infant deaths. This work was initiated to determine the performance of acylcarnitine profiling for detecting this variant, to determine its frequency in BC, and to determine if it is associated with sudden infant deaths in this population.
Methods:
Newborn screening cards from all BC First Nations infants in 2004 and all sudden unexpected deaths in BC First Nations infants (1999-2009) were genotyped for the CPT1A p.P479L variant and linked to archival acylcarnitine data.
Results:
The CPT1A p.P479L variant is frequent in BC First Nations but is not evenly distributed, with higher rates in coastal regions (up to 25% homozygosity) with historically increased infant mortality. There is also an overrepresentation of p.P479L homozygotes in unexpected infant deaths from these regions, with an odds ratio of 3.92 (95% confidence interval: 1.69-9.00). Acylcarnitine profiling will identify p.P479L homozygotes with a 94% sensitivity and specificity.
Conclusions:
The CPT1A p.P479L variant is common to some coastal BC First Nations, and homozygosity for this variant is associated with unexpected death in infancy. The high frequency of this variant in a wide range of coastal aboriginal communities, however, suggests a selective advantage, raising the possibility that this variant may have differing impacts on health depending on the environmental or developmental context.
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