Tim-1基因多态性与儿童原发性肾病综合征免疫抑制剂或激素耐药性的关系

Relationship between Tim-1 gene polymorphism and immunosuppressive or steroid resistance in children with primary nephrotic syndrome

目的:探讨T细胞免疫球蛋白域黏蛋白域蛋白-1(Tim-1)基因多态性与儿童原发性肾病综合征(PNS)免疫抑制剂或激素耐药性的关系。方法:研究组80患儿为郑州市第七人民医院2020年6月至2021年1月收治的PNS患儿,均采用免疫抑制剂或激素冲击治疗,根据治疗反应分为敏感型(n=65)及耐药型(n=15);选取同期体检健康者60例为对照组,分析两组Tim-1基因多态性,并对免疫抑制剂或激素耐药性的独立影响因素进行分析。结果:两组Tim-1基因启动子区域的-1454G/A基因型频率和等位基因频率比较,差异有统计学意义(P<0.05);两组Tim-1基因外显子4插入/缺失(ins/del)基因型和等位基因频率比较,差异无统计学意义(P>0.05)。敏感型与耐药型患儿Tim-1基因启动子区域的-1454G/A基因型的分布频率比较,差异显著(P<0.05),等位基因频率的差异无统计学意义(P>0.05);敏感型与耐药型患儿Tim-1基因外显子4 ins/del基因型的分布频率及等位基因频率比较,差异无统计学意义(P>0.05);Tim-1基因启动子区域的-1454G/A基因型GA是PNS患儿免疫抑制剂或激素耐药性的独立危险因素(P<0.05)。结论:Tim-1基因启动子区域的-1454G/A基因多态性可作为PNS的遗传易感性标记,且与PNS患儿免疫抑制剂或激素耐药性密切相关性。

Objective:To explore the relationship between T-cell immunoglobulin domain mucin domain protein-1(Tim-1)gene polymorphism and immunosuppressive or steroid resistance in children with primary nephrotic syndrome(PNS).Methods:Eighty children with PNS admitted to the 7th People’s Hospital of Zhengzhou from June 2020 to January 2021 were selected as the study group.All of them were treated with immunosuppressive agents or steroid pulse therapy.According to treatment response,they were divided into sensitive type(n=65)and drug-resistant type(n=15).Meanwhile,60 healthy individuals were selected as the control group.Tim-1 gene polymorphisms and the independent factors influencing immunosuppressive agent or steroid resistance were analyzed.Results:The genotype frequencies and allele frequencies at-1454G/A of Tim-1 gene promoter region in the two groups were significantly different(P<0.05).There was no significant difference in allele frequency(P>0.05),while the genotype frequencies and allele frequencies at 4 ins/del of Tim-1 gene exon region showed no significant differences between the two groups(P>0.05).There was a significant difference between sensitive and drug-resistant children in genotype frequency at-1454G/A of Tim-1 gene promoter region(P<0.05).There was no significant difference in allele frequency(P>0.05).There was no significant difference in the distribution frequency and allele frequency of Tim-1 exon 4 ins/del genotype between sensitive and drug-resistant children(P>0.05).Genotype GA at-1454G/A of Tim-1 gene promoter region was an independent risk factor for immunosuppressive agent or steroid resistance children with PNS(P<0.05).Conclusions:Gene polymorphism at-1454G/A of Tim-1 gene promoter region may be genetic susceptibility mark of PNS,and is closely related to immunosuppressive agent or steroid resistance in children with PNS.