title: Carnitine palmitoyltransferase I and sudden unexpected infant death in British Columbia First Nations.
abstract: 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.
authors.affiliation: Departmens of aPathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia. gsinclair@cw.bc.ca
authors.forename: Graham B
authors.initials: GB
authors.lastname: Sinclair
authors.forename: Sorcha
authors.initials: S
authors.lastname: Collins
authors.forename: Oana
authors.initials: O
authors.lastname: Popescu
authors.forename: Deborah
authors.initials: D
authors.lastname: McFadden
authors.forename: Laura
authors.initials: L
authors.lastname: Arbour
authors.forename: Hilary D
authors.initials: HD
authors.lastname: Vallance
mesh_terms: D001955:British Columbia; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007231:Infant, Newborn; D012307:Risk Factors; D013398:Sudden Infant Death / Q000235:genetics*
chemical_list: D002334:Carnitine O-Palmitoyltransferase