Genetic polymorphisms within tumor necrosis factor gene promoter region: A role for susceptibility to ventilator-associated pneumonia

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• 作者：Antigoni Kotsaki^a ; Maria Raftogiannis^a ; Christina Routsi^b ; Fotini Baziaka^a ; Anastasia Kotanidou^b ; Anastasia Antonopoulou^c ; Stylianos E. Orfanos^c ; Chrisostomos Katsenos^d ; Pantelis Koutoukas^a ; Diamantis Plachouras^a ; Konstantinos Mandragos^d ; Evangelos J. Giamarellos-Bourboulis^a ; ^{egiamarel@med.uoa.gr}
• 关键词：Genetic polymorphisms ; Tumor necrosis factor ; Ventilator associated pneumonia ; Cytokines
• 刊名：Cytokine
• 出版年：2012
• 期刊代码：97_10434666
• 类别：imm
• 出版时间：August, 2012
• 卷：59
• 期：2
• 页码：358-363
• 文件大小：406 K

摘要

Debatable findings exist among various studies regarding the impact of single nucleotide polymorphisms (SNPs) within the promoter region of the tumor necrosis factor (TNF) gene for susceptibility to infections. Their impact was investigated in a cohort of mechanically ventilated patients who developed ventilator-associated pneumonia (VAP). Two-hundred and thirteen mechanically ventilated patients who developed VAP were enrolled. Genomic DNA was extracted and SNPs at the 鈭?76, 鈭?08 and 鈭?38 position of the promoter region of the TNF gene were assessed by restriction fragment length polymorphisms. Monocytes were isolated from 47 patients when they developed sepsis and stimulated by bacterial endotoxin for the production of TNF伪 and of interleukin-6 (IL-6). Patients were divided into two groups; 166 patients bearing only wild-type alleles of all three studied polymorphisms; and 47 patients carrying at least one A allele of the three studied SNPs. Time between start of mechanical ventilation and advent of VAP was significantly shorter in the second group than in the first group (log-rank: 4.416, p: 0.041). When VAP supervened, disease severity did not differ between groups. Stimulation of TNF伪 and of IL-6 was much greater by monocytes for patients carrying A alleles. Carriage of at least one A allele of the three studied SNPs at the promoter region of the TNF-gene is associated with shorter time to development of VAP but it is not associated with disease severity. Findings may be related with a role of the studied SNPs in the production of pro-inflammatory cytokines.