Neuregulin-1 high-producer genotype is associated with a decreased risk of admission to the neonatal intensive care unit.
BACKGROUND
Neuregulin (NRG1) is a developmental growth factor and homozygous C allele carriers at the NRG221533 locus are at reduced risk for developmental disability.


OBJECTIVE
To explore whether 1) the NRG221533 CC genotype is associated with a decreased likelihood of neonatal intensive care unit (NICU) admission; 2) NRG1 is present in the infant's systemic circulation; and 3) to comparatively investigate two additional proposed high-producer single nucleotide polymorphisms (SNPs) for the cytokines interleukin 6 (-572) and interleukin 10 (-1082), examining both gene product and the association for admission to the NICU.


METHODS
IL6 and IL10 protein was measured in umbilical cord blood by a multiplex sandwich immunoassay and NRG1 by ELISA. Infants were screened for SNPs IL6 (-572), IL10 (-1082), and NRG221533. We defined IL6 (C), IL10 (G) and NRG1 (C) as high-producer alleles based on published data.


METHODS
Unselected single-center convenience sample of 97 newborns with a gestational age of 25-33 weeks (N=18), 34-36 weeks (N=17), 37-38 weeks (N=28), and 39-41 weeks (N=34).


METHODS
Prematurity (<37 completed weeks) and admission to NICU.


RESULTS
The SNP NRG221533 CC genotype was associated with reduced admission to the NICU, even after adjustment for confounders. Adjustment for high IL6 levels reduced the protective effect. NRG1 levels tended to increase with advancing gestational age. Unexpectedly, we found lower IL6 and IL10 levels in infants homozygous for the IL6 (C) and IL10 (G) alleles, and no associations between IL10 (-1082) and IL6 (-572) genotype and prematurity or admission to NICU.


CONCLUSIONS
The NRG221533 CC genotype might be protective in newborns. The protective effect might not be directly related to increased systemic NRG levels.
Pleickhardt
Elizabeth P
EP
Division of Newborn Medicine, Floating Hospital for Children at Tufts Medical Center, Boston, MA 02111, USA.
Celandine
Andrew
A
Davis
Jonathan M
JM
Chen
Minghua
M
Schürmann
Peter
P
Dörk
Thilo
T
Dammann
Christiane E L
CE
Dammann
Olaf
O
D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D020890:Neuregulin-1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D012306:Risk; D015854:Up-Regulation
C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C094131:NRG1 protein, human; D020890:Neuregulin-1; D016753:Interleukin-10