Lower prevalence of IL-4 receptor α-chain gene 1902G variant in very-low-birth-weight infants with necrotizing enterocolitis

Background/Purpose: Altered production of immunoregulatory cytokines is associated with the development of necrotizing enterocolitis (NEC) in preterm very low-birth-weight (VLBW) infants. According to data obtained in adults, functional genetic polymorphisms influence cytokine production capacity. The aim of this study was to evaluate whether functional polymorphisms of interleukin (IL)-1beta, IL-4 receptor alpha-chain (IL-4ra), IL-6, and IL-10 genes might be associated with the risk of NEC in VLBW infants. Methods: Dried blood spot samples of 46 VLBW infants with NEC were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Samples from 90 VLBW infants without NEC were used as controls. Results: Infants with NEC carried the mutant variant of IL-4ra less frequently than controls (0.125 v 0.224; P < .05) even after adjustment for risk factors of NEC. No significant differences were found in the allelic frequencies of IL-1 beta, IL-6, and IL-10 genes between NEC and control infants. Conclusions: Carrier state of IL-4ra mutant allele might be associated with lower risk of NEC in VLBW infants. This genetic variant is associated with enhanced IL-4 effect. IL-4 is a major regulator of Th1-Th2 shift. The authors hypothesize that infants carrying the IL-4ra mutant allele might have Th2 skewness that might defend against the development of NEC. (C) 2003 Elsevier Inc. All rights reserved.