Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis

• Published in: Pediatric research Vol. 62; no. 2; pp. 188 - 190
• Main Authors: MOONEN, Rob M. J, PAULUSSEN, Aimee D. C, SOUREN, Nicole Y. P, KESSELS, Alfons G. H, RUBIO-GOZALBO, M. Estela, VILLAMOR, Eduardo
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-08-2007
• Subjects: Arginine - blood; Biological and medical sciences; Carbamoyl-Phosphate Synthase (Ammonia) - genetics; Carbamoyl-Phosphate Synthase (Ammonia) - metabolism; Case-Control Studies; Enterocolitis, Necrotizing - blood; Enterocolitis, Necrotizing - enzymology; Enterocolitis, Necrotizing - epidemiology; Enterocolitis, Necrotizing - genetics; Epidemiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; General aspects; Genetic Predisposition to Disease; Gestational Age; Humans; Incidence; Infant, Newborn; Infant, Premature - blood; Infant, Premature - metabolism; Male; Medical sciences; Odds Ratio; Other diseases. Semiology; Polymorphism, Single Nucleotide; Public health. Hygiene; Public health. Hygiene-occupational medicine; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Human; Phosphates; Pediatrics; Genetic variability; Enzyme; Necrotizing enterocolitis; Genotype; Genetic determinism; Epidemiology; Carbamoyl; Newborn; Ligases; Risk factor; Digestive diseases; Genetics; Intestinal disease; Public health; Polymorphism
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/PDR.0b013e3180a0324e

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.