蒙、汉族儿童原发性肾病综合征TIM-3基因及IFN-γ检测的意义

摘要

目的 研究TIM-3基因多态性及γ干扰素(IFN-γ)水平与儿童原发性肾病综合征(PNS)发病的相关性.方法 采用病例对照研究,选取汉族PNS患儿21例,蒙古族(祖籍三代以上均为蒙古族)、汉族(祖籍三代以上均为汉族)健康体检各20例为对照组;采用PCR–限制性片段多态性分析方法,分析检测PNS患儿和对照组的T细胞免疫球蛋白黏蛋白分子3(TIM-3)基因外显子-574 A/C的单核苷酸多态性,比较基因型及等位基因频率;采用酶联免疫吸附法检测血IFN-γ水平,并分析其变化.结果 汉族和蒙古族正常对照组之间TIM-3基因外显子-574A/C位点基因型(AA、AC、CC)分布差异无统计学意义(P=0.741);两组间等位基因频率差异也无统计学意义(P=0.655).将汉族和蒙古族正常对照组合并与汉族PNS患儿进行比较,汉族PNS患儿-574A/C位点AA、AC和CC基因型频率分别为9.52%、28.57%和61.90%,与40例正常对照组儿童的基因型分布差异有统计学意义(P=0.017);汉族PNS患儿的C等位基因频率为76.2%,高于正常对照组(50.0%),差异有统计学意义(P=0.005),与A等位基因个体比较,C等位基因携带者儿童发生PNS的风险增加3.20倍(95%CI:1.39～7.37).汉族PNS、汉族以及蒙古族正常对照组之间血清IFN-γ水平的差异无统计学意义(P>0.05).结论 TIM-3基因外显子-574A/C的单核苷酸多态性可能与儿童PNS的发病相关;IFN-γ与儿童原发性肾病综合征的发病无明显相关性.%Objective To explore the association of T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) gene polymorphism and IFN-γ levels with the incidence of primary nephrotic syndrome (PNS) in children. Methods A case-control study was conducted and 21 Han patients with PNS were selected and included in case group. Meanwhile, 20 each from Mongolian and Han were selected and assigned into control group and at least three generations of their family members were from the same nationality. PCR-restriction fragment polymorphism analysis was used to detect and analyze single nucleotide polymorphisms of exon -574A/C in TIM-3 gene in PNS children and controls. Also the genotype and allele frequencies between the two groups were compared. Enzyme linked immunosorbent assay (ELISA) was used to detect the level of serum IFN-γ and its changes was analyzed. Results There was no significant difference in the distribution of genotypes (AA, AC, CC) of exon -574A/C in TIM-3 gene between the Han and Mongolian subgroups in control group (P=0.741). Neither did the allele frequency between the two groups (P=0.655). Compared with control group (Han and Mongolian), the frequencies of AA, AC and CC genotypes were 9.52%, 28.57% and 61.90% respectively in -574A/C loci of the Han nationality children with PNS. There was significant difference in genotypes distribution between the two groups (P=0.017). The frequency of C allele in PNS children of Han nationality was 76.2% which was higher than that in normal control group (50%), and the difference was statistically significant (P=0.005). Compared with A allele carriers, the risk of PNS in C allele carriers increased by 3.20 times (95%CI: 1.39～7.37). There were no significant differences in serum IFN-γ among the Han nationality with PNS, Han and Mongolian normal control groups (P>0.05). Conclusion The single nucleotide polymorphism of the exon -574A/C of TIM-3 gene may be related to the pathogenesis of PNS in children. In addition, IFN-γ is not associated with the incidence of primary nephrotic syndrome in children.