Genetic association study of tumor necrosis factor-alpha with sepsis and septic shock in Thai pediatric patients.

OBJECTIVES: To evaluate the association between the genetic polymorphism of the tumor necrosis factor-alpha (TNF-α) gene and the development of sepsis and septic shock in Thai pediatric patients and to investigate the clinical impacts of TNF-α polymorphisms in this population. METHODS: To perform this genetic association study, a prospective analysis of pediatric patients (age < 18 years) with clinical sepsis/septic shock was conducted. All clinical data were collected by pediatric intensive care experts, and genetic analyses were performed at a central laboratory. A single nucleotide polymorphism (SNP) located in the 5'-promoter region at position -308 was genotyped and the results were associated with clinical phenotypes. RESULTS: A total of 167 Thai individuals were investigated, 66 of which were pediatric patients with sepsis/septic shock and 101 were healthy controls. Interestingly, we could not identify an association between sepsis and -308 (G/A) polymorphism, which have previously been demonstrated to be a major SNP associated with sepsis in several Caucasian populations, since there was no frequency difference between cases and controls. CONCLUSIONS: In this report, the major TNF-α polymorphism (-308) was not associated with clinical sepsis/septic shock in Thais. This information will be important for future analyses to identify the role of TNF-α as a genetic risk for the development of immunopathology underlying several diseases in Asia.

Estudo de associação genética entre fator de necrose tumoral alfa e sepse e choque séptico em pacientes pediátricos tailandeses / Genetic association study of tumor necrosis factor-alpha with sepsis and septic shock in Thai pediatric patients

OBJETIVOS: Avaliar a associação entre o polimorfismo genético do fator de necrose tumoral alfa (TNF-α) e o desenvolvimento de sepse e choque séptico em pacientes pediátricos tailandeses e investigar o impacto clínico de polimorfismos do TNF-α nessa população. MÉTODOS: Para a realização deste estudo de associação genética, foram analisados prospectivamente pacientes pediátricos (idade < 18 anos) com sepse clínica/choque séptico. Todos os dados foram coletados por especialistas em terapia intensiva pediátrica e as análises genéticas foram realizadas em um laboratório central. Um polimorfismo de nucleotídeo único [single nucleotide polymorphism (SNP)], localizado na região promotora 5' na posição -308, foi genotipado e os resultados foram associados a fenótipos clínicos. RESULTADOS: Foram investigados 167 indivíduos tailandeses, dos quais 66 eram pacientes pediátricos com sepse/choque séptico e 101 eram controles saudáveis. Curiosamente, não foi possível identificar associação entre sepse e o polimorfismo -308 (G→A), um dos principais SNPs anteriormente associado à sepse em várias populações caucasianas, visto que não houve diferença de frequência entre casos e controles. CONCLUSÕES: Neste estudo, o principal polimorfismo do TNF-α -308 não esteve associado à sepse clínica/choque séptico na população tailandesa. Essa informação é importante para futuras análises que busquem identificar a função do TNF-α como risco genético para o desenvolvimento de imunopatologia subjacente a várias doenças no continente asiático.

OBJECTIVES: To evaluate the association between the genetic polymorphism of the tumor necrosis factor-alpha (TNF-α) gene and the development of sepsis and septic shock in Thai pediatric patients and to investigate the clinical impacts of TNF-α polymorphisms in this population. METHODS: To perform this genetic association study, a prospective analysis of pediatric patients (age < 18 years) with clinical sepsis/septic shock was conducted. All clinical data were collected by pediatric intensive care experts, and genetic analyses were performed at a central laboratory. A single nucleotide polymorphism (SNP) located in the 5'-promoter region at position -308 was genotyped and the results were associated with clinical phenotypes. RESULTS: A total of 167 Thai individuals were investigated, 66 of which were pediatric patients with sepsis/septic shock and 101 were healthy controls. Interestingly, we could not identify an association between sepsis and -308 (G→A) polymorphism, which have previously been demonstrated to be a major SNP associated with sepsis in several Caucasian populations, since there was no frequency difference between cases and controls. CONCLUSIONS: In this report, the major TNF-α polymorphism (-308) was not associated with clinical sepsis/septic shock in Thais. This information will be important for future analyses to identify the role of TNF-α as a genetic risk for the development of immunopathology underlying several diseases in Asia.