Association between the A/A genotype at the lymphotoxin-alpha+250 site and increased mortality in children with positive blood cultures.

Introduction: Tumor necrosis factor-alpha has been implicated in the hemodynamic manifestations of sepsis. Genetic polymorphisms located in the first intron of the lymphotoxin-alpha gene have been associated with increased secretion of tumor necrosis factor-alpha. We hypothesized that bacteremic children with the high secretor genotype, AA, have higher levels of tumor necrosis factor-alpha and a worse outcome.

Methods: Genotypic analysis was performed in children with bacteremia using polymerase chain reaction amplification and restriction enzyme digestion. The serum tumor necrosis factor-alpha levels were measured by enzyme-linked immunosorbent assay technique.

Results: Genotypic frequencies at the lymphotoxin-alpha+250 site were 11 of 34 (0.32) AA, 16 of 34 (0.47) GA, and 7 of 34 (0.21) GG. Serum tumor necrosis factor-alpha levels were 324 +/- 124 pg/mL in bacteremic children with the AA genotype at the lymphotoxin-alpha+250 site compared with 92 +/- 59 pg/mL in bacteremic children with the AG genotype (p < .001) and 92 +/- 21 pg/mL in bacteremic children with the GG genotype (p < .001). Eight of 11 bacteremic children with the AA genotype died compared with 3 of 16 bacteremic children with the GA genotype (p < .001) and zero of seven bacteremic children with the GG genotype (p < .001).

Conclusion: The AA genotype at the lymphotoxin-alpha+250 site is associated with higher serum tumor necrosis factor-alpha levels and a higher mortality in children with bacteremia.