title: Evidence for an association between infant mortality and homozygosity for the arctic variant of carnitine palmitoyltransferase 1A.
abstract: Infant mortality in Alaska is highest among Alaska Native people from western/northern Alaska, a population with a high prevalence of a genetic variant (c.1436C>T; the arctic variant) of carnitine palmitoyltransferase 1A (CPT1A).
  
  
  
  We performed an unmatched case-control study to determine the relationship between the arctic variant and infant mortality. The cases were 110 Alaska Native infant deaths from 2006 to 2010 and the controls were 395 Alaska Native births from the same time period. In addition to the overall analysis, we conducted two subanalyses, one limited to subjects from western/northern Alaska and one limited to infants heterozygous or homozygous for the arctic variant.
  
  
  
  Among western/northern Alaska residents, 66% of cases and 61% of controls were homozygous (adjusted odds ratio (aOR): 2.5; 95% confidence interval (CI): 1.3, 5.0). Among homozygous or heterozygous infants, 58% of cases and 44% of controls were homozygous (aOR: 2.3; 95% CI: 1.3, 4.0). Deaths associated with infection were more likely to be homozygous (OR: 2.9; 95% CI: 1.0-8.0). Homozygosity was strongly associated with a premorbid history of pneumonia, sepsis, or meningitis.
  
  
  
  Homozygosity for the arctic variant is associated with increased risk of infant mortality, which may be mediated in part by an increase in infectious disease risk. Further studies are needed to determine whether the association we report represents a causal association between the CPT1A arctic variant and infectious disease-specific mortality.Genet Med 18 9, 933-939.
authors.affiliation: Alaska Division of Public Health, Anchorage, Alaska, USA.|Present address: EpiVac Consulting, Anchorage, Alaska, USA.
authors.forename: Bradford D
authors.initials: BD
authors.lastname: Gessner
authors.affiliation: Alaska Division of Public Health, Anchorage, Alaska, USA.|Present address: EpiVac Consulting, Anchorage, Alaska, USA.
authors.forename: Thalia
authors.identifier: 0000-0001-9563-6391
authors.initials: T
authors.lastname: Wood
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Monique A
authors.initials: MA
authors.lastname: Johnson
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Carolyn Sue
authors.identifier: 0000-0003-1078-979X
authors.initials: CS
authors.lastname: Richards
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, USA.|Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: David M
authors.identifier: 0000-0002-4340-4908
authors.initials: DM
authors.lastname: Koeller
mesh_terms: D000413:Alaska; D000072957:Alaska Natives / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D003141:Communicable Diseases / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D007198:Indians, North American; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D008297:Male; D008581:Meningitis / Q000235:genetics / Q000401:mortality; D015997:Neonatal Screening; D011014:Pneumonia / Q000235:genetics / Q000401:mortality; D012307:Risk Factors; D018805:Sepsis / Q000235:genetics / Q000401:mortality
chemical_list: C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase
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