血栓调节蛋白单核苷酸多态性与脓毒症的相关性研究

The association of single nucleotide polymorphism of thrombomodulin and sepsis

目的研究血栓调节蛋白(thrombomodulin,TM)的基因型及其等位基因的分布频率,分析可能与脓毒症相关的单核苷酸多态性(single nucleotide polymorphism,SNP)。方法采用单碱基延伸PCR技术和DNA测序方法,检测132例无血缘关系的体检健康人群和172例脓毒症患者的TM的SNPs,比较分析各组间基因型及等位基因的分布频率,以及这些SNPs位点是否与脓毒症的易感性有关。结果健康广西人群rs1962C/T的多态性分布与非洲人相比差异有统计学意义,rs3176123G/T、rs6082986G/A以及rs1042580C/T的基因多态性与欧洲人、北京人、日本人和非洲人相比差异有统计学意义。脓毒症组rs1042580C/T位点的基因型频率分布CT和TT均高于对照组,基因型频率之间差异有统计学意义,但等位基因频率差异无统计学意义。其余六个位点rs13306848C/T、rs1962C/T、rs3176123G/T、rs6082986G/A、rs6113909G/A以及rs1042579G/A的基因型频率和等位基因分布,在两组间差异无统计学意义。结论TM的单核苷酸多态性在不同地区、种族人群之间的基因型及等位基因分布存在差异;TM的rs1042580C/T基因位点的基因型频率与脓毒症易感性有关。

Objective To study the allele and genotype distribution of thrombomodulin （TM） and to ex- plore the single nucleotide polymorphism （SNP） which may be associated with sepsis. Methods Single base extension PCR and DNA sequencing were used to measure the single nucleotide polymorphism of TM in 172 pa- tients with sepsis and 132 health controls without consanguinity relationship. The distribution frequencies of the genotype and allele were compared among different groups in order to evaluate whether these gene loci of TM were associated with sepsis susceptibility. Results Comparison of rs1962C/T polymorphism distribution between Guangxi health population and Africans yielded that there was statistically significant difference, and there were statistically significant differences in comparison of rs3176123G/T, rs6082986G/A and rs1042580C/ T polymorphisms among Guangxi population and Europeans, Beijing population, Japanese and Africans. The frequency distribution of CT genotype and TT genotype of rs1042580C/T polymorphism in sepsis group were higher than those of the control group, comparison of genotype frequencies of sepsis group with those of con- trol group, there were statistically significant differences, but there was no statistically significant difference in comparison of allele frequency. There were no statistically significant differences in genotype frequencies and allele distribution at other six loci rs13306848C/T, rs1962C/T, rs3176123G/T, rs6082986G/A, rs6113909G/ A and rs1042579G/A between the sepsis group and the control group. Conclusion There were significant differences in genotypes and alielic distribution of TM SNPs among ethnic groups in different regions; the gen otype frequencies of TM rs1042580C/T was associated with susceptibility of sepsis.