Genetic polymorphisms of CD14, toll-like receptor 4, and caspase-recruitment domain 15 are not associated with necrotizing enterocolitis in very low birth weight infants.
OBJECTIVE
Inadequate response of the innate immune system to bacterial antigens present in the intestinal flora may play a role in the development of necrotizing enterocolitis (NEC). Pattern recognition receptors such as CD14, toll-like receptor (TLR) 4, and caspase-recruitment domain (CARD) 15 bind bacterial lipopolysaccharide and peptidoglycan, and their activation leads to production of inflammatory cytokines. Our aim was to evaluate whether single nucleotide polymorphisms (SNPs) of CD14, TLR4, and CARD15 are associated with the risk of NEC in very low birth weight (VLBW) infants.


METHODS
We determined the CD14 C-260T, TLR4 A +896G, C +1196T, and CARD15 G +2722C, C +2104T, 3020insC functional SNPs in dried blood samples from 118 VLBW infants (of those, 41 developed NEC) and from 146 healthy term newborns using polymerase chain reaction and restriction fragment length polymorphism methods. We tested the association between genotype and risk of NEC.


RESULTS
No significant differences were found in the prevalence of CD14 -260T, TLR4 +896G, +1196T, and CARD15 +2722C, +2104T, 3020insC alleles between VLBW infants and healthy term newborns (P = NS). The frequencies of investigated genotypes were similar in infants with and without NEC (P = NS). Furthermore, we did not find any association between genotype and prematurity or sepsis, which are important risk factors of NEC.


CONCLUSIONS
Carrier state of the tested CD14, TLR4, and CARD15 SNPs is not associated with NEC risk in VLBW infants.
Szebeni
Beáta
B
First Department of Pediatrics, Semmelweis University, Budapest, Hungary. szebeni@gyer1.sote.hu
Szekeres
Roxána
R
Rusai
Krisztina
K
Vannay
Adám
A
Veres
Gábor
G
Treszl
András
A
Arató
András
A
Tulassay
Tivadar
T
Vásárhelyi
Barna
B
D020345:Enterocolitis, Necrotizing / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D053473:Nod2 Signaling Adaptor Protein; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D051197:Toll-Like Receptor 4