Evidence for an association between infant mortality and a carnitine palmitoyltransferase 1A genetic variant.

Abstract:

OBJECTIVE:Alaska Native and other circumpolar indigenous populations have historically experienced high infant mortality rates, for unknown reasons. Through routine newborn screening, Alaskan and Canadian indigenous infants have been found to have a high frequency of a single sequence variant (c.1436C→T) in the gene coding for carnitine palmitoyltransferase type 1A (CPT1A). We sought to determine whether these 2 findings were related. METHODS:As part of a quality control exercise at the Alaskan Newborn Metabolic Screening Program, we conducted genotyping for 616 consecutively born, Alaska Native infants and reviewed their medical records. We conducted an ecological analysis comparing Census area-level variant CPT1A allele frequency and historical Alaska Native infant, postneonatal, and neonatal mortality rates. RESULTS:Infant death was identified for 5 of 152 infants homozygous for the c.1436C→T sequence variant (33 deaths per 1000 live births), 2 of 219 heterozygous infants (9 deaths per 1000 live births), and 0 of 245 infants carrying no copies of the variant allele (χ(2) = 9.2; P = .01). All 7 cases of infant death had some evidence of an infectious process at the time of death, including 5 with respiratory infections. Census areas with the highest frequency of the variant allele had the highest historical infant, postneonatal, and neonatal mortality rates. CONCLUSIONS:Our data provide preliminary evidence that a highly prevalent CPT1A variant found among Alaska Native and other indigenous circumpolar populations may help explain historically high infant mortality rates. Larger definitive studies are needed.

journal_name

Pediatrics

journal_title

Pediatrics

authors

Gessner BD,Gillingham MB,Birch S,Wood T,Koeller DM

doi

10.1542/peds.2010-0687

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

945-51

issue

5

eissn

0031-4005

issn

1098-4275

pii

peds.2010-0687

journal_volume

126

pub_type

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