转化生长因子β1基因rs2317130单核苷酸多态性与结核病易感性的关联分析

Association between single nucleotide polymorphism of transforming growth factorβ1 gene rs2317130 and susceptibility to tuberculosis

目的探究转化生长因子β1(transforming growth factorβ1,TGF-β1)基因单核苷酸多态性(single nucleotide polymorphism,SNP)与结核病易感性的关系,为结核病的诊断和治疗提供更多的参考依据。方法通过病例-对照(case-control)研究方法,以深圳市第三人民医院1533例确诊的活动性结核病患者作为病例组(男980例,女553例),选取同期在该院体检的1445例人员作为健康对照组。通过飞行时间质谱仪(TOF-MS)检测TGF-β1基因6个SNP位点rs2317130、rs17516265、rs8110090、rs3087453、rs2278422、rs1800469基因型,通过比较两组间SNP等位基因频率差异,初步筛选出与结核病易感性相关联的SNP位点。用结核分枝杆菌标准株H37Rv刺激不同基因型的健康人外周血单个核细胞(peripheral blood mononuclear cell,PBMCs),ELISA检测上清中TGF-β1含量,进一步验证TGF-β1基因SNP位点与结核易感性的关系。结果在6个SNP位点中发现仅rs2317130 C>T位点等位基因频率在活动性结核组和对照组中差异有统计学(P<0.05),结核病患者rs2317130 C>T位点C等位基因频率显著增高(OR=1.14;95%CI=1.03~1.26;P<0.01),其他5个SNP等位基因频率在两组之间差异无统计学意义(P>0.05)。此外,ELISA实验结果表明,rs2317130 SNP位点CC纯合子基因型的患者TGF-β1表达量显著高于其他基因型(CT杂合子和TT纯合子基因型),TGF-β1表达量上调可加速结核病发展,进一步证实rs2317130位点C等位基因为结核易感基因。结论TGF-β1基因rs2317130 C>T位点与结核易感性相关,其C等位基因为结核易感基因,即携带C等位基因人群患结核风险升高。

Objective To explore the relationship between single nucleotide polymorphism(SNP)of transforming growth factorβ1(TGF-β1)and susceptibility to tuberculosis in the Han population in Southern China,and provide more reference basis for the diagnosis and treatment of tuberculosis.Methods By case-control method,1533 patients with active tuberculosis confirmed in the Third People's Hospital of Shenzhen were selected as the case group(980 males and 553females),and 1445 healthy patients who underwent physical examination in the hospital during the same period were selected as the control group.Six SNP loci of TGF-β1 gene rs2317130,rs17516265,rs8110090,rs3087453,rs2278422 and rs1800469 genotypes were detected by time-of flight mass spectrometry,compared the SNP allele frequency difference between two groups and then the SNP loci associated with TB susceptibility were preliminarily screened out.The peripheral blood mononuclear cells(PBMCs)of healthy people with different genotypes were stimulated by H37Rv standard strain of Mycobacterium tuberculosis.Detected the content of TGF-β1 in supernatant,and then the relationship between SNP sites of TGF-β1 gene and TB susceptibility was further verified.Results Among the 6 SNP loci,only rs2317130 C>T loci were found to have statistically significant differences in allele frequency between active tuberculosis group and control group(P<0.05).The C allele frequency of rs2317130 C>T locus was significantly increased in tuberculosis patients(OR=1.14;95%CI=1.03-1.26;P<0.01),while the other 5 SNP allele frequencies showed no statistically significant difference between the two groups(P>0.05).Moreover,ELISA results showed that TGF-β1 expression was significantly higher in patients with CC homozygous genotype at rs2317130 SNP site than in other genotypes(CT heterozygous genotype and TT homozygous genotype).TGF-β1 expression was up-regulated to accelerate the development of tuberculosis.It was further confirmed that the C allele of rs2317130 locus was a TB susceptibility gene.Conclusion The C>T locus of rs2317130 of TGF-β1 gene is associated with TB susceptibility,and its C allele is a TB susceptibility gene,people with the C allele have an increased risk of developing TB.