Polymorphism of tumor necrosis factor-alpha and risk and severity of bronchopulmonary dysplasia among very low birth weight infants.
Polymorphism of tumor necrosis factor-alpha and risk and severity of bronchopulmonary dysplasia among very low birth weight infants.
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DOI：
10.1542/peds.114.2.e243
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发表时间：
2004-08-01
期刊：
影响因子：
8
通讯作者：
Buhimschi, Irina
中科院分区：
文献类型：
--
作者：
Kazzi, S Nadya J;Kim, U Olivia;Buhimschi, Irina
背景：患有支气管肺发育不良（BPD）的早产儿在气管吸出物中表现出炎症指数的长期升高。肿瘤坏死因子-α（TNF-α）是炎症反应的中心介质。TNF-α-308和TNF-α +250的含腺嘌呤等位基因与TNF-α水平升高相关，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可能通过压倒性的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可能会降低BPD.OBJECTIVE的风险和/或严重程度：以确定是否等位基因的TNF-α发挥作用的易感性和/或BPD. METHODS的严重程度在极低出生体重儿BPD.METHODS：出生体重<或=1250 g的婴儿。基因型分析应用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测BPD患儿外周血DNA。（孕36周时吸入氧分数>0.21，n = 51）的胎龄较短（平均值+/- SD：27 +/- 4 vs 29 +/- 2周）和出生体重（853 +/- 184 vs 997 +/- 193 g）低于无BPD的婴儿（n = 69）。在婴儿组中，α-光敏素-250和TNF-α-308的基因型分布相似。然而，AA和GA TNF-alpha-238基因型在BPD婴儿中发生的可能性要比在无BPD婴儿中小得多。与轻度BPD婴儿相比，重度BPD婴儿中TNF-α-238的腺嘌呤等位基因不存在，中度或重度BPD婴儿中TNF-α-238的腺嘌呤等位基因的发生率显著降低。结论：TNF-α-238的腺嘌呤等位基因可能降低BPD的发病风险和严重程度。
BACKGROUND: 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.OBJECTIVE: To determine whether alleles of TNF-alpha play a role in the susceptibility and/or severity of BPD among very low birth weight infants.METHODS: 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.RESULTS: 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).CONCLUSION: The adenine allele of TNF-alpha-238 may reduce the risk and severity of BPD.