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UBC Theses and Dissertations

The role of the carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant in Inuit infant and child health outcomes in Nunavut Collins, Sorcha


Nunavut leads the country for a number of adverse early child health outcomes, including infant hospitalizations for lower respiratory tract infection (LRTI; ~306/1,000), otitis media (85%) and infant mortality (21.5/1,000). The p.P479L (c.1436C>T, rs80356779) variant of carnitine palmitoyltransferase 1A (CPT1A), an enzyme required for long-chain fatty acid oxidation in the liver, pancreas, lymphocytes and other tissues, is prevalent in northern Indigenous populations of Canada. Although evidence is limited, the p.P479L variant has been associated with childhood infectious illness, hypoglycemia, seizures and with unexpected infant death and infant death due to infection. This dissertation investigated the association of p.P479L variant with infant and child morbidity (up to five years) in the context of relevant prenatal, postnatal and socioeconomic variables in a cohort of 2523 Inuit children living in Nunavut born from Jan-2010 to Dec-2013. The results demonstrate that the CPT1A p.P479L variant was associated with infectious illness in early childhood including LRTI admission, otitis media and gastroenteritis, after adjustment for socioeconomic and other confounding variables. In considering the potential effect on fatty acid oxidation and possible risk for hypoglycemia, I also determined that the incidence of neonatal hypoglycemia was higher in term Inuit newborns than expected, and, although not statistically significant, p.P479L homozygous and heterozygous newborns had higher incidence of neonatal hypoglycemia than non-carriers. Taken together, these results suggest that children homozygous for the p.P479L variant may be more susceptible to infectious illness compared to non-carriers and may be more likely to experience hypoglycemia in the first days of life. My results replicate and expand on previous, smaller studies. Multidisciplinary local input and community engagement is indicated to determine if routine neonatal glucose screening and/or other management is indicated for Inuit infants. Further studies are needed to understand the role of the p.P479L variant in infection susceptibility, immune and inflammatory response and vaccination effectiveness in Inuit communities.

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