Kazzi S Nadya J, Kim U Olivia, Quasney Michael W, Buhimschi Irina
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Hutzel Women's Hospital, 4707 St Antoine, Detroit, Michigan 48201, USA.
Pediatrics. 2004 Aug;114(2):e243-8. doi: 10.1542/peds.114.2.e243.
Preterm infants with bronchopulmonary dysplasia (BPD) exhibit prolonged elevation of inflammatory indices in their tracheal aspirates. Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of the inflammatory response. The adenine-containing alleles of TNF-alpha-308 and lymphotoxin-alpha+250 have been associated with increased levels of TNF-alpha, whereas the adenine allele of TNF-alpha-238 produces lower levels of TNF-alpha after stimulation. High levels of TNF-alpha may promote chronic inflammation by overwhelming counter-regulatory mechanisms and may lead to the development of BPD. Low levels of TNF-alpha may decrease the risk and/or severity of BPD.
To determine whether alleles of TNF-alpha play a role in the susceptibility and/or severity of BPD among very low birth weight infants.
Infants with birth weights of < or =1250 g were included. Genotypic analyses (polymerase chain reaction-restriction fragment length polymorphism assays) were performed with DNA extracted from whole-blood samples.
Infants who developed BPD (fraction of inspired oxygen at postconceptional age of 36 weeks of >0.21, n = 51) had a younger gestational age (mean +/- SD: 27 +/- 4 vs 29 +/- 2 weeks) and lower birth weight (853 +/- 184 vs 997 +/- 193 g) than did infants without BPD (n = 69). The genotypic distributions of lymphotoxin-alpha+250 and TNF-alpha-308 were comparable among the groups of infants. However, the AA and GA TNF-alpha-238 genotypes were much less likely to occur among infants with BPD than among infants without BPD. The adenine allele of TNF-alpha-238 was absent among infants with severe BPD and occurred significantly less often among infants with moderate or severe BPD, compared with infants with mild BPD. The number of adenine alleles of TNF-alpha-238 was correlated inversely with the severity of BPD (r = -.341).
The adenine allele of TNF-alpha-238 may reduce the risk and severity of BPD.
患有支气管肺发育不良（BPD）的早产儿气管吸出物中的炎症指标持续升高。肿瘤坏死因子-α（TNF-α）是炎症反应的核心介质。TNF-α -308含腺嘌呤的等位基因和淋巴毒素-α +250与TNF-α水平升高有关，而TNF-α -238的腺嘌呤等位基因在刺激后产生较低水平的TNF-α。高水平的TNF-α可能通过压倒反调节机制促进慢性炎症，并可能导致BPD的发展。低水平的TNF-α可能降低BPD的风险和/或严重程度。
确定TNF-α等位基因在极低出生体重儿BPD的易感性和/或严重程度中是否起作用。
纳入出生体重≤1250g的婴儿。用从全血样本中提取的DNA进行基因分型分析（聚合酶链反应-限制性片段长度多态性分析）。
发生BPD的婴儿（孕龄36周时吸入氧分数>0.21，n = 51）与未发生BPD的婴儿（n = 69）相比，胎龄更小（平均±标准差：27±4 vs 29±2周），出生体重更低（853±184 vs 997±193g）。淋巴毒素-α +250和TNF-α -308的基因分型分布在各婴儿组中具有可比性。然而，与未发生BPD的婴儿相比，发生BPD的婴儿中AA和GA TNF-α -238基因型出现的可能性要小得多。严重BPD婴儿中不存在TNF-α -238的腺嘌呤等位基因，与轻度BPD婴儿相比，中度或重度BPD婴儿中该等位基因出现的频率明显更低。TNF-α -238的腺嘌呤等位基因数量与BPD的严重程度呈负相关（r = -0.341）。
TNF-α -238的腺嘌呤等位基因可能降低BPD的风险和严重程度。
