The T1405N Carbamoyl Phosphate Synthetase Polymorphism Does Not Affect Plasma Arginine Concentrations in Preterm Infants

A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1) has been associated with changes in plasma concentrations of L-arginine in term and near term infants but not in adults. In preterm infants homozygosity for the CPS1 Thr1405 variant (CC genotype) was associated with an increased risk of having necrotizing enterocolitis (NEC). Plasma L-arginine concentrations are decreased in preterm infants with NEC.To examine the putative association between the CPS1 T1405N polymorphism and plasma arginine concentrations in preterm infants.Prospective multicenter cohort study. Plasma and DNA samples were collected from 128 preterm infants (<30 weeks) between 6 and 12 hours after birth. Plasma amino acid and CPS1 T1405N polymorphism analysis were performed.Distribution of genotypes did not differ between the preterm (CC:CA:AA = 55.5%:33.6%:10.9%, n = 128) and term infants (CC:CA:AA = 54.2%:35.4%:10.4%, n = 96). There was no association between the CPS1 genotype and plasma L-arginine or L-citrulline concentration, or the ornithine to citrulline ratio, which varies inversely with CPS1 activity. Also the levels of asymmetric dimethylarginine, and symmetric dimethylarginine were not significantly different among the three genotypes.The present study in preterm infants did not confirm the earlier reported association between CPS1 genotype and L-arginine levels in term infants

Distribution of the <i>CPS1</i> genotypes for the polymorphism at position 1405 in healthy term infants.

<p>Results are expressed as absolute numbers of patients (percentage). CC denotes homozygosity for the C-encoded Thr1405 variant, AA homozygosity for the A-encoded Asn1405 variant, and AC heterozygosity for this polymorphism.</p

Urea cycle intermediates and methylated arginine per genotype.

<p>Results of plasma concentrations (µmol/l) are expressed as median [interquartile range].</p><p>Statistical analysis between the genotypes. NS = not significant.</p

Baseline patient characteristics.

<p>Results are expressed as mean (SD), median [interquartile range], or <i>absolute numbers of patients (percentage)</i>.</p><p>Statistical analyses between the different genotypes. NS = not significant.</p

Distribution of the <i>CPS1</i> genotypes for the polymorphism at position 1405 in preterm infants.

<p>Results are expressed as absolute numbers of patients (percentage). CC denotes homozygosity for the C-encoded Thr1405 variant, AA homozygosity for the A-encoded Asn1405 variant, and AC heterozygosity for this polymorphism.</p