Candidate gene analysis in pathogenesis of surgically and non-surgically treated necrotizing enterocolitis in preterm infants

Abstract

Necrotizing enterocolitis (NEC) is one of the most severe and unpredictable complications of prematurity. There are two possible mechanisms involved in the pathogenesis of NEC: individual inflammatory response and impaired blood flow in mesenteric vessels with secondary ischemia of the intestine. The aim of this study was to evaluate the possible relationship between polymorphisms: Il-1β 3953C>T, Il-6 −174G>C and −596G>A, TNFα −308G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il-1RN VNTR 86 bp) and three polymorphisms that may participate in arteries tension regulation and in consequence in intestine blood flow impairment: eNOS (894G>T and −786T>C) and END-1 (5665G>T) and NEC in 100 infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. In study population, 22 (22%) newborns developed NEC. Surgery-requiring NEC was present in 7 children. Statistical analysis showed 20-fold higher prevalence of NEC in infants with the genotype TT [OR 20 (3.71–208.7); p = 0.0004] of eNOS 894G>T gene polymorphism. There was a higher prevalence of allele C carriers of eNOS 786T>C in patients with surgery-requiring NEC [OR 4.881 (1.33–21.99); p = 0.013]. Our investigation did not confirm any significant prevalence for NEC development in another studied genotypes/alleles. This study confirms the significant role of polymorphisms that play role in intestine blood flow. Identifying gene variants that increase the risk for NEC development may be useful in screening infants with inherent vulnerability and creating strategies for individualized care.Electronic supplementary materialThe online version of this article (doi:10.1007/s11010-017-3135-5) contains supplementary material, which is available to authorized users.

Necrotizing enterocolitis in preterm infants: state of the intestinal barrier, features of vitamin D metabolism and their regulation

“…• эндотелиальная NO-синтаза -путем выработки оксида азота, регулирует кровоток и целостность в слизистой оболочке кишечника [17], • гепарин-связывающий эпидермальный факторусиливает кишечный кровоток, снижает апоптоз клеток, стимулирует миграцию и пролиферацию энтероцитов [17].…”

“…Некротизирующий энтероколит (НЭК) является смертельным заболеванием, при котором современные диагностические инструменты недостаточны для доклинического выявления и предотвращения НЭК, а ранние прогностические биомаркеры могут быть полезны для выявления детей с высоким риском развития НЭК -этот тезис констатируют исследователи во всем мире [17,18]. Однако существуют сложности поиска диагностических маркеров, которые часто заключаются в ограниченной численности выборки, в частности, Hoff sten A, и соавторы обследовали 11 новорожденных с НЭК и исследовали у них 189 воспалительных, онкологических и сосудистых протеомных биомаркеров.…”

Single nucleotide vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) in the pathogenesis of prematurity complications

“…Such a finding highlights the possible role of VDR genetic variation on the overall interaction between vitamin D and the TLR4 cascade. An increasing number of reports have placed emphasis on the genetic predisposition of preterm infants to NEC [56][57][58][59][60][61] . However, due to lack of extensive research and coherence of results, validating studies remain necessary to elucidate the relationship between gene variation and NEC 62 .…”

Genetic predisposition to necrotizing enterocolitis in premature infants: Current knowledge, challenges, and future directions

“…As excessive inflammation is a hallmark of NEC, many investigators have examined the relationship of several pro-inflammatory cytokine gene polymorphisms and NEC, with varying results. Treszl et al 17, 18 , Heninger et al 19 , Henderson et al 20 , and Szpecht et al 22 have examined functional variants of several pro-inflammatory cytokines (including tumor necrosis factor-alpha, interleukin (IL)-1β, IL-4 receptor α-chain, IL-6, IL-18, and IL-10) and found no evidence of association of these genes with NEC. In contrast, Franklin et al 21 reported a positive association between IL-6 (rs1800795) variant and NEC in Caucasian neonates; while Tian et al 48 found a positive association between IL17F (rs763780) variant and NEC in a Chinese cohort.…”

“…In another study, Szpecht et al 22 more directly evaluated nitric oxide pathways by measuring polymorphisms of eNOS in 100 preterm infants, 22 of whom had NEC. They found that eNOS 894G>T polymorphism was more common in infants with NEC (OR 20, 95% CI 3.71–208.7, p=0.0004), and the eNOS 786T>C was increased in infants with surgical NEC (OR 4.88, 95% CI 1.33–21.99, p=0.013).…”