FOXP3基因多态性与儿童ITP发病及进展的相关性研究

目的通过对儿童免疫性血小板减少症（immune thrombocytopenia,ITP）患儿Forkhead Box P3（FOXP3）基因单核苷酸多态性检测、了解儿童ITP发病并随访疾病进展情况,探讨FOXP3基因多态性与儿童ITP发生、发展的关系,以期为开展儿童ITP的靶向治疗提供一定理论依据。方法 328例ITP患儿作为实验组,219例健康志愿者作为对照组。实验组根据病程及转归又分为两组（病程在12个月以内组、病程在12个月以上组）。利用Sequenom SNP位点分型检测方法分别检测FOXP3基因rs3761547、rs3761548、rs2232365 3个位点单核苷酸多态性。结果 1）rs2232365位点在性别年龄均匹配实验组AG基因型频率较正常对照组明显增高（P=0.013）,其他2个位点单核苷酸多态性在两组之间差异无统计学意义。2）rs3761547位点在12个月以上组GG基因型及G等位基因较12月以内组明显增高（P=0.008,0.001）;rs2232365位点A与G基因频率在不同病程间差异有统计学意义（P=0.033）。结论 FOXP3 rs2232365位点携带AG基因型可能为ITP发病的易感因素。携带FOXP3 rs3761547 GG基因型及G等位基因、rs2232365位点G等位基因的ITP患儿更易发展为慢性,病程迁延。rs2232365位点单核苷酸多态性与儿童ITP的发生发展均相关,可能是疾病机制的关键。

FOXP3 gene polymorphism may contribute to the onset and progress of children immune thrombocytopenia

Objective To investigate the association between FOXP3 gene polymorphism and the onset and progress of children immune thrombocytopenia（ ITP）,to explore the pathogenesis of childhood ITP. Methods A total of 328 patients of initial onset of ITP and 219 healthy individuals were enrolled into study group and controls group,respectively. FOXP3 polymorphisms： rs3761547,rs3761548 and rs2232365 were genotyped by the Sequenom SNP genotyping method. Patients were divided into two groups according to diagnosis and results of follow-up： ＂disease course exceeding 12 months＂and＂disease course within 12 months＂. Results The genotype rs2232365 AG was significantly higher in age-and sex-matched study group comparing to control group（ P = 0. 013）. Patients with rs2232365 G allele,rs3761547 GG genotype or G allele showed significantly higher in disease course exceeding 12 months sub-group than in disease course within 12 months sub-group（ P = 0. 008,0. 001,0. 033 respectively）. Conclusion The genotype rs2232365 polymorphism was associated with the pathogenesis of ITP; rs3761547 GG genotype and G alleles / rs2232365 G allele may tend to have longer course and worse progress in children ITP. rs2232365 polymorphism was associated with progress of children ITP,which may play an important role in children ITP.