Genetic polymorphisms and the risk of infection following esophagectomy. positive association with TNF-alpha gene -308 genotype.
OBJECTIVE
To examine the association of single nucleotide polymorphisms (SNPs) in inflammation-related genes in the development of infections following esophagectomy.


BACKGROUND
Genetic polymorphisms for immunoregulatory cytokines may explain individual variation in response to trauma. Esophagectomy is associated with a high risk of postoperative infection and sepsis, and this study explored a number of SNPs in cytokine genes and their relationship to postoperative infection.


METHODS
: In a prospective analysis of 197 patients with esophageal cancer undergoing resection, 55 developed postoperative infections. DNA was extracted and genotyping was performed for polymorphisms in genes encoding TNF-alpha, IL-1beta, IL-1 receptor antagonist, IL-10, and Toll-like receptor 4 (TLR-4) using Taqman chemistry and PCR/RFLP. In a blinded analysis, the cohort with infections was compared with the no complication cohort (n = 114) and a cohort that had noninfective complications (n = 28).


RESULTS
No differences in polymorphisms for IL-1beta, IL-1 RN, IL-10, and TLR-4 genes were observed across groups. The frequency of TNF-alpha -308 GG homozygotes was significantly (P = 0.021) higher in the postoperative infection group. The G allele was significantly higher in the postoperative infection group compared with the no complication group (P = 0.017) and other complication group (P = 0.013). By multivariate analysis, this polymorphism as well as age and body mass index were predictors of infection.


CONCLUSIONS
The TNF-alpha -308A allele has been shown to be associated with higher circulating levels of TNF-alpha and the -308 G allele is a comparative low secretor allele. We propose that the polymorphism in the promotor region of TNF-alpha gene may lead to altered expression and a possible suboptimal activity of TNF-alpha in persons with GG genotypes, and these data suggest a link with infection following major surgery.
Azim
Kaukab
K
Department of Clinical Surgery and Dublin, of Molecular Medicine Center, St. Jame's Hospital, Dublin, Ireland.
McManus
Ross
R
Brophy
Karen
K
Ryan
Aoife
A
Kelleher
Dermot
D
Reynolds
John V
JV
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001424:Bacterial Infections / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015992:Body Mass Index; D004273:DNA, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000601:surgery; D016629:Esophagectomy / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011183:Postoperative Complications; D011446:Prospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10