Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients.
The innate recognition of microbial components and subsequent activation of cytokine network are important in the pathophysiology of sepsis. Recently, functional gene polymorphisms in molecules associated with these responses were demonstrated. On the other hand, it has been claimed that there are ethnic differences in genetic polymorphisms. This study investigated toll-like receptor (TLR) 4, CD14, tumor necrosis factor (TNF)-alpha and -beta, and interleukin (IL)-10 gene polymorphisms in 197 Japanese critically ill patients and 214 healthy control subjects to evaluate the influence of these polymorphisms on clinical outcome. No Japanese participant carrying TLR4Asp299Gly or Thr399Ile was detected. No association of CD14-159C/T polymorphisms with genotype frequency or sepsis mortality was observed. Frequency of TNF-alpha-308 GA genotype was significantly higher in the sepsis group than in the control group and TNF-alpha-308GA and IL-10-592CC genotypes were related to poor outcome of sepsis. Ethnic differences in genetic variations are very important issues and the frequencies in this study differ from those previously reported in Caucasians. In conclusion, this study may indicate that TNF-alpha-308G/A and IL-10-592C/A polymorphisms involved in subsequent activation of cytokine network had a larger effect on clinical outcome in patients with sepsis than TLR4Asp299Gly, Thr399Ile, and CD14-159C/T polymorphisms associated with the initial host-microbial interaction.
Nakada
Taka-Aki
TA
Department of Emergency and Critical Care Medicine, Chiba University, 1-8-1 Inohana, Chuo, Chiba, Japan. taka.nakada@nifty.com
Hirasawa
Hiroyuki
H
Oda
Shigeto
S
Shiga
Hidetoshi
H
Matsuda
Ken-Ichi
K
Nakamura
Masataka
M
Watanabe
Eizo
E
Abe
Ryuzo
R
Hatano
Masahiko
M
Tokuhisa
Takeshi
T
D018806:APACHE; D000328:Adult; D000368:Aged; D016638:Critical Illness; D005260:Female; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007564:Japan; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018805:Sepsis / Q000235:genetics* / Q000276:immunology; D012727:Sex Characteristics; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D018950:Lipopolysaccharide Receptors; D008233:Lymphotoxin-alpha; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10