TIM-1基因多态性与原发性肾病综合征的关系

Association between TIM-1 Gene Polymorphisms and Primary Nephrotic Syndrome in Children

目的研究TIM-1基因多态性与儿童原发性肾病综合征(PNS)的相关性。方法采用病例对照研究,选取PNS患儿57例,应用PCR-限制性片段长度多态性分析、PCR-聚丙烯酰胺凝胶电泳分析、基因测序技术检测PNS患儿和144例健康儿童(健康对照组)的TIM-1基因启动子区-1454G/A的SNP与外显子4 ins/del多态性,计算基因型和等位基因频率。结果健康对照组TIM-1启动子区-1454位G/G、G/A和A/A基因型频率分别为0.608、0.328、0.064,而PNS组频率分别为0.772、0.228、0.000,其基因型频率与健康对照组比较差异有统计学意义(χ2=6.561,P=0.038),且PNS组患儿携带-1454G等位基因的频率增高(OR=2.295,95%CI:1.199～4.390,P=0.011);健康对照组TIM-1外显子4 del/del、del/ins和ins/ins基因型频率分别为0.611、0.340、0.049,而PNS组频率分别为0.579、0.368、0.053,其基因型频率与健康对照组比较差异无统计学意义(χ2=0.176,P=0.916)。结论 TIM-1基因启动子-1454G/A的单核苷酸多态性可能与儿童PNS的易感性相关。

Objective To assess the genetic association between the TIM-1 polymorphisms and primary nephrotic syndrome（PNS）in children. Methods A case-control study was performed in 57 cases of PNS patients and 144 cases of healthy controls.Associations between the TIM-1 polymorphisms and PNS were examined by using polymerase chain reaction-restriction fragment length polymorphism analysis,PCR-polyacrylamide gel electrophoresis and gene sequencing technology,genotype and allele frequencies were calculated;the relationship was found between comparison groups. Results The genotype frequencies of G/G,G/A,A/A in the TIM-1 gene-1454G/A region were 0.608,0.328,0.064 in healthy children and 0.772,0.228,0.000 in children with PNS.There was significant difference in genotype frequencies between patients and controls（χ~2=6.561,P=0.038）.Carriers of the-1454G single-nucleotide polymorphism（SNP） were increased among PNS patients as compared with controls（OR=2.295,95%CI：1.199-4.390,P=0.011）.The genotype frequencies of del/del,del/ins and ins/ins in the TIM-1 exon 4 ins/del region were 0.611,0.340,0.049 in healthy children and 0.579,0.368,0.053 in children with PNS.There was no significant difference in genotype distribution between patients and controls（χ~2=0.176,P=0.916）. Conclusion TIM-1 gene-1454 SNP might be associated with susceptibility to the development of PNS.