title: Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis.
abstract: A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1) has been correlated with low plasma concentrations of L-arginine in neonates. As plasma L-arginine concentrations are decreased in premature infants with necrotizing enterocolitis (NEC), we hypothesized that the CPS1 T1405N polymorphism would correlate with the presence of NEC. We analyzed the CPS1 genotypes for the T1405N polymorphism in 17 preterm infants (<or=30 wk and <1500 g) with established NEC, 34 preterm infants without NEC, and 25 healthy term infants. Distribution of genotypes did not differ between the NEC population (CC:AC:AA = 70.6%:23.5%:5.9%) and the preterm control group (CC:AC:AA = 41.2%:35.3%:23.5%; p = 0.110) or the term group (CC:AC:AA = 44%:48%:8%; p = 0.228). The C allele frequency was 82.4% in NEC and 58.8% in preterm control infants (p = 0.018) and analysis for linear trend demonstrated that incidence of NEC increased with the number of C alleles (p = 0.037). The CC genotype was associated with an increased risk of NEC in the preterm infants [odds ratio (OR) = 3.43, 95% confidence interval (CI): 1.01-11.49, p = 0.048), when compared with the grouped together AA/AC genotypes. These data suggest that the CPS1 T1405N polymorphism may be associated with the risk of NEC in preterm infants.
authors.affiliation: Department of Pediatrics, University Hospital of Maastricht, 6202 AZ Maastricht, The Netherlands.
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Moonen
authors.forename: Aimee D C
authors.initials: AD
authors.lastname: Paulussen
authors.forename: Nicole Y P
authors.initials: NY
authors.lastname: Souren
authors.forename: Alfons G H
authors.initials: AG
authors.lastname: Kessels
authors.forename: M Estela
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Villamor
mesh_terms: D001120:Arginine / Q000097:blood; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D020345:Enterocolitis, Necrotizing / Q000097:blood / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000378:metabolism*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D001120:Arginine; D002222:Carbamoyl-Phosphate Synthase (Ammonia)