Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study.
The p.Thr1406Asn (rs1047891) polymorphism of the carbamoyl-phosphate synthetase 1 (CPS1) gene has been linked to functional consequences affecting the downstream availability of the nitric oxide precursor L-arginine. L-arginine concentrations are decreased in preterm infants with necrotizing enterocolitis (NEC). In this multicenter prospective study, we investigated the association of the p.Thr1406Asn polymorphism with NEC in 477 preterm infants (36 cases of NEC) from 4 European neonatal intensive care units (Maastricht, Las Palmas de Gran Canaria, Mantova, and Milan). Allele and genotype frequencies of the p.Thr1406Asn polymorphism did not significantly differ between the infants with and without NEC. In contrast, the minor A-allele was significantly less frequent in the group of 64 infants with the combined outcome NEC or death before 34 weeks of corrected gestational age than in the infants without the outcome (0.20 vs. 0.31, P = 0.03). In addition, a significant negative association of the A-allele with the combined outcome NEC or death was found using the dominant (adjusted odds ratio, aOR: 0.54, 95% CI 0.29-0.99) and the additive (aOR 0.58, 95% CI 0.36-0.93) genetic models. In conclusion, our study provides further evidence that a functional variant of the CPS1 gene may contribute to NEC susceptibility.
Department of Pediatrics, Zuyderland Medical Center Heerlen, 6130 MB, The Netherlands.|Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, 6202 AZ, The Netherlands.
Rob M
RM
Moonen
Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 20122, Italy.
Giacomo
G
Cavallaro
Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, 6202 AZ, The Netherlands.
Maurice J
MJ
Huizing
Department of Pediatrics, Hospital Universitario Materno-Infantil de Canarias, Las Palmas de Gran Canaria, 35016, Spain.
Gema E
GE
González-Luis
Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 20122, Italy.
Fabio
F
Mosca
Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), Maastricht, 6202 AZ, The Netherlands.
Eduardo
E
Villamor
D000483:Alleles; D001120:Arginine / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics*; D015897:Comorbidity; D020345:Enterocolitis, Necrotizing / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D007363:Intensive Care Units, Neonatal; D007558:Italy / Q000453:epidemiology; D008297:Male; D008957:Models, Genetic; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome
D001120:Arginine; D002222:Carbamoyl-Phosphate Synthase (Ammonia)