Carnitine Palmitoyltransferase I and Sudden Unexpected Infant Death in British Columbia First Nations

Abstract

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.

Carnitine palmitoyltransferase 1A P479L and infant death: policy implications of emerging data

“…1,3,4 The ORs in the 4 studies reviewed here are high, of similar magnitude and statistically significant. However, the case sample sizes in all four studies are small (n = 7, n = 35, n = 51, and n = 110, respectively), 1, 4, 3, 8 and the OR confidence intervals are wide, providing imprecise estimates of the actual magnitude of the association.…”

“…3 They found that frequencies of P479L homozygosity varied widely across the 3 regions (Table 1). Additionally, they found that the C0/(C16+C18) ratios in newborns with P479L homozygosity were significantly higher than in newborns heterozygous and homozygous for the reference variant (p < 0.0001).…”

“…3 Below, we examine the strength of the evidence and conclusions presented in each of these studies separately, and then assess the collective evidence according to epidemiologic criteria for a causal association. 24 …”

“…However, the ratios were well below those found for infants with classic CPT1A deficiency (50% percentile in the mid-20’s for P479L homozygotes compared to 105 for infants with classic CPT1A deficiency 16 ), and no difference was seen between the ratios of the 11 P479L homozygotes who suffered infant death and the ratios of the 227 infants who did not. 3 …”

“…Four epidemiological studies in Alaska and Canada have reported a statistical association between P479L homozygosity and infant death, suggesting that the genotype may have important public health significance. 1,3,4,7,8 …”