Association of the CPT1A p.P479L Metabolic Gene Variant With Childhood Respiratory and Other Infectious Illness in Nunavut

Frontiers in Pediatrics

article

Sorcha A. Collins¹  Cheryl Rockman-Greenberg²  Laura Arbour¹  Sharon Edmunds³  Gwen Healey Akearok⁴  J. Robert Thompson⁵  Anders C. Erickson⁶  Elske Hildes-Ripstein²  Amber Miners⁷  Martin Somerville⁸  David M. Goldfarb⁹ 

[1] Department of Medical Genetics, University of British Columbia;Department of Pediatrics and Child Health, University of Manitoba;Department of Research, Nunavut Tunngavik Inc.;Qaujigiartiit Health Research Centre;Cadham Provincial Laboratory;School of Population and Public Health, University of British Columbia;Department of Health;Department of Laboratory Medicine and Pathobiology University of Toronto;Department of Pathology and Laboratory Medicine, University of British Columbia

关键词: Indigenous;    Inuit;    carnitine palmitoyltransferase 1A;    infectious illness;    p.P479L arctic variant;    respiratory tract infection in children;   

DOI  :  10.3389/fped.2021.678553

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, Canada, and Greenland. CPT1A is a fatty acid oxidation enzyme expressed in the liver, immunocytes and other tissues, and is needed to use fats for energy during fasting. Previous association of the variant with early childhood infectious illness and infant death has been challenged because of sample size and limited adjustment for confounders. We evaluated whether the p.P479L variant is associated with infectious illness in Inuit children of Nunavut, Canada. Methods: We conducted a retrospective clinical chart review of 2,225 Inuit children (0–5 years) for infectious illness (including otitis media, gastroenteritis, and hospital admission for LRTI), prenatal, perinatal, and socioeconomic indicators, subsequently linking to CPT1A genotype. Multivariable logistic regression adjusted for birth characteristics, breastfeeding, maternal smoking, food insecurity, and socioeconomic indicators. Results: Overall, 27% of children were hospitalized for LRTI, 86% had otitis media and 50% had gastroenteritis. The p.P479L allele frequency was 0.82. In multivariable analysis, p.P479L homozygosity was associated with LRTI admission (aOR:2.88 95%CI:1.46–5.64), otitis media (aOR:1.83, 95%CI:1.05–3.21), and gastroenteritis (aOR:1.74, 95%CI:1.09–2.77), compared to non-carriers. Conclusion: Children homozygous for the p.P479L variant were more likely to experience infectious illness than non-carriers, including hospitalization for respiratory tract infections. Given the role of CPT1A in immunocytes, our findings indicate that more study is needed to determine if there is a role of the variant in immune response. Continued Inuit involvement is essential when considering next steps.

【 授权许可】

CC BY