温州地区汉族儿童脓毒症与Toll样受体基因多态性

Gene polymorphisms of Toll-like receptors in Chinese Han children with sepsis in Wenzhou

目的研究温州地区汉族脓毒症（sepsis）患儿TLR4（Asp299Gly、Thr399Ile）和TLR2（Arg753Gln）基因多态性的分布特征及与脓毒症严重程度的相关性。方法采用病例一对照研究和测序法对2006年1月至2008年6月期问收住温州医学院附属育英儿童医院的59例脓毒症患儿、38例严重脓毒症患儿（包括脓毒性休克20例）和57例健康对照组儿童进行TLR4（Asp299Gly、Thr399Ile）和TLR2（Arg753Gln）基因多态性检测，计算多态位点在三组中的分布频率，按Hardy—Weinberg遗传平衡定律检验，比较不同组别之间各等位基因频率和基因型频率差异是否有显著性。结果59例脓毒症组患儿、38例严重脓毒症组患儿和57例健康对照组儿童中均未发现TLR4突变基因（Asp299Gly、Thr399Ile）；在38例严重脓毒症组患儿中发现2例TLR2突变基因（Arg753Gln），且均为金黄色葡萄球菌感染休克死亡病例，而59例脓毒症组患儿和57例健康对照组儿童中均未发现TLR2突变基因（Arg753Gln）。结论TLR4基因（Asp299Gly、Thr39911e）多态性与温州地区汉族儿童脓毒症易感性无明显相关性；TLR2基因（Arg753Gln）多态性是否与温州地区汉族儿童致命性阳性菌感染有关，尚需积累更多的儿童脓毒症病例进行研究。

Objective Sepsis remains a serious clinical problem because of high morbidity and mortality. The importance of Toll-like receptors （TLRs） for the induction of immune responses against sepsis was demonstrated in humans. The present study aimed to probe the gene polymorphisms of TLR4 （Asp299Gly and Thr399Ile） and TLR2 （Arg753Gln） in patients with sepsis among Chinese HaM children in Wenzhou, and investigate the correlation with sepsis. Method This study was conducted as a case-control study. Using polymerase chain reaction and DNA sequencing, gene polymorphisms of TLR4 （Asp299Gly and Thr399Ile） and TLR2 （Arg753Gln） in 59 children with sepsis, 38 children with severe sepsis （ including 20 septic shock） and 57 healthy controls were analyzed. Hardy-Weinberg method of statistics was used to compare the frequency of genotypes alleles among three groups. Result The mutant genotypes of TLR4 gene （Asp299Gly and Thr399Ile） were not found among sepsis, septic shock and control groups. In severe sepsis group, the Arg753Gln TLR2 polymorphism occurred in 2 out of 38 severe sepsis patients and both of the subjects with the TLR2 Arg753Gln polymorphism had fatal staphylococcal infections. Conclusion TLR4 gene （Asp299Gly and Thr399IIe） polymorphisms may not be correlated with susceptibility to sepsis among Chinese HaM children in Wenzhou. The fact that only 2 out of 38 severe sepsis patients had Arg753Gln TLR2 polymorphism suggests that a larger sample size is needed because of the rarity of the TLR2 allele among Chinese HaM children in Wenzhou.