Adcock K, Hedberg C, Loggins J, Kruger T E, Baier R J
Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA.
Genes Immun. 2003 Sep;4(6):420-6. doi: 10.1038/sj.gene.6363986.
Chronic lung disease (CLD) in premature newborns is associated with increased concentrations of inflammatory cytokines in tracheal aspirates (TA). We determined if polymorphisms of cytokine genes influence the risk of developing CLD by genotyping 178 mechanically ventilated very low birth weight (VLBW) infants for the tumor necrosis factor-alpha (TNF-alpha) -308 G/A, transforming growth factor-beta(1) (TGF-beta(1)) +915 G/C and monocyte chemoattractant protein-1 (MCP-1) -2518 A/G polymorphisms. Genomic DNA was isolated from TA and genotypes determined by restriction length polymorphism. There was no effect of any of these polymorphisms on the development of CLD (29 vs 23%, P=0.371, TNF-alpha -308 AA/AG vs TNF-alpha -308 GG; 23 vs 26%, P=0.681, MCP-1 -2518 GG/AG vs MCP-1 -215-8 AA; 24 vs 24%, P=0.978, TGF-beta(1) +915 CG vs TGF-beta(1) +915 GG). TA IL-8 and MCP-1 concentrations were not different between genotype groups. Infants with the TNF-alpha -308 A allele had increased risk of IVH (RR 2.07; 95% CI 1.02-4.18, P=0.041) and infants with the TGF-beta(1) +915 C allele were at greater risk of death (32 vs 9%, P=0.016). These data suggest that these polymorphisms do not play a significant role in determining risk for CLD in preterm infants, but may play a role in other complications in the neonatal period.
早产新生儿慢性肺部疾病（CLD）与气管吸出物（TA）中炎性细胞因子浓度升高有关。我们通过对178例机械通气的极低出生体重（VLBW）婴儿进行肿瘤坏死因子-α（TNF-α）-308 G/A、转化生长因子-β(1)（TGF-β(1)）+915 G/C和单核细胞趋化蛋白-1（MCP-1）-2518 A/G多态性基因分型，来确定细胞因子基因多态性是否影响CLD的发生风险。从TA中分离基因组DNA，并通过限制性片段长度多态性确定基因型。这些多态性对CLD的发生均无影响（29%对23%，P=0.371，TNF-α -308 AA/AG对TNF-α -308 GG；23%对26%，P=0.681，MCP-1 -2518 GG/AG对MCP-1 -215-8 AA；24%对24%，P=0.978，TGF-β(1) +915 CG对TGF-β(1) +915 GG）。各基因型组之间TA白细胞介素-8和MCP-1浓度无差异。携带TNF-α -308 A等位基因的婴儿发生脑室内出血的风险增加（相对危险度2.07；95%可信区间1.02 - 4.18，P=0.041），而携带TGF-β(1) +915 C等位基因的婴儿死亡风险更高（32%对9%，P=0.016）。这些数据表明，这些多态性在确定早产儿CLD风险方面不起重要作用，但可能在新生儿期的其他并发症中起作用。
