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Toll样受体4基因多态性与脓毒症的关系

Study of the relationship between TLR4 gene polymorphism and sepsis

摘要:

目的 用SPSS 16.0进行统计学分析,多组比较采用方差分析,两两比较采用采用LSD-t检验和秩和检验.结果 深圳地区G-杆菌感染患者TRL4 2244,2299位点均发生不同程度的变异,与文献报道的健康中国人群相比,2299A→G基因型频率有明显差异(P<0.05).但无论从死亡率、感染性休克发生率、ICU平均住院时间、ICU平均费用进行SNP阳性和阴性两组比较,均无统计学意义(P值分别为0.741,0.405,0.160,0.129).结论 TRL4基因5'调控区2244,2299位点确实在深圳地区脓毒症患者中存在广泛存在的遗传学变异,2299A→G基因型频率可能具有地区和人群分布差异.影响脓毒症患者病情发展和预后的因素较复杂,基因多态性可能仅仅是众多的影响因素之一.

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abstracts:

Objective To study the 2244G→A, 2299 A→G single nucleotide polymorphism (SNP) in the 5' regulatory regions of Toll-like receptor 4 (TLR4) in patients with Gram negative bacteria infection in Shenzhen locality, and to discuss the occurrence, course and prognosis of patients with sepsis. Method Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the genotype of TLR4. After the whole blood DNA of patient was extracted and PCR was amplified, the products were 500bp and 599 bp, and were cut by endonuclease Mae Ⅱ and Sph Ⅰ respectively to determine the SNP 2244G→A and 2299 A→G in TLR4. These two kinds of allele frequencies were statistically calculated in all patients. In the meantime, the incidence of septic shock, average hospitalized days, cost and prognosis of all patients were recorded. Statistical analysis was performed with SPSS version 16 software. ANOVA was used for comparison among multiple groups, and t -test and Sighed rank test were used for paired comparison. Results The 2299 and 2244 sites in the 5' regulatory regions of TLR4 gene of patients with Gram negative bacteria infection in Shenzhen locality had various degrees of changes in single nucleotide. Compared with the documented data from Chinese people in general, there was a significant difference in 2299A→G genotype frequency in residents of Shenzhen locality ( P < 0.05). But there were no statistically significant difference in mortality, incidence of septic shock, average days of ICU stay or ICU cost between TLR4 SNP positive and negative groups of patients. Conclusions There is a wide range of genetic variation in the 2299 and 2244 sites in the 5' regulatory regions of TLR4 among citizens of Shenzhen locality with unique distribution. The 2299A→G genotype frequency probably has differences in distribution and population. The pathogenesis and the prognostic factors of sepsis are complicated, whereas the gene polymorphism may be just one of the factors affecting the prognosis of patients with Gram negative bacteria infection.

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