Carbamyol phosphate synthetase 1 gene (4217C>A) polymorphism and its relation to low plasma arginine level among preterm with necrotizing enterocolitis; a single center Egyptian study

Abstract

Necrotizing entero-colitis [NEC] is the most prevailing and devastating acquired gastrointestinal emergency among premature neonates.1 Despite the observable worthy advancement in the care of small preemies over the foregoing decades, NEC; as yet; exists as a foremost leading predisposition for as certainable increase in mortality and poor outcome among tiny preemies in neonatal intensive-care-units [NICU].2 Although numerous predisposing factors have been well-settled, the explicit patho-etiological mechanisms of NEC is still unclear. It has been emphasized that the combination of immaturity & underdevelopment of intestinal motility, digestive ability, intestinal barriers, immune defense and intestinal microcirculatory regulation with an abnormal intestinal microbial colonization in the presence of genetic predisposition were the probable patho-etiological predispositions for development of NEC.1,3 Nitric oxide (NO); which is synthesized from amino acid (L-arginine) by NO synthetase enzyme (NOS); is the principle inhibitory neurotransmitter in the gastro-intestinal system. It has a crucial role in maintaining the vasodilator tone, regulate mucosal blood flow, and maintain intestinal mucosal integrity and barrier function. 4,5 L-arginine, which is declared as a functionally essential amino-acid, is one of the urea-cycle intermediates that produced by the action of carbamyol-phostphate synthetase 1(CPS1) enzyme.6 It has been noticed that the unavailability of L-arginine was associated with limitation in NO production and increased predisposition to NEC. In addition, numerous studies disclosed that plasma arginine concentration was declined in preemies with NEC.7–9 Moreover, it has been disclosed that arginine supplementation decreases the liability for NEC development.[7] CPS1 enzyme; which is encoded by CPS1 gene on chromosome (2q34); is the rate-limiting enzyme catalyzing