CASP3基因单核苷酸多态性与中国儿童川崎病的相关性研究  

Association of CASP3 gene single nucleotide polymorphisms with Kawasaki disease in Chinese children patients

作　　者：彭茜[1] 陈昌辉[1] 吴青[1] 李波[1] 廖静[1] 罗彩丹[1] 胡小平[1] 郑植[1] 邓燕[1] 张渝[1] 

机构地区：[1]四川省人民医院儿科,成都610072

出　　处：《中华医学遗传学杂志》2013年第2期180-184,共5页Chinese Journal of Medical Genetics

基　　金：四川省卫生厅课题（120079）

摘　　要：目的分析半胱氨酸蛋白酶3基因（caspase-3，CASP3）多态性与中国儿童川崎病（Kawasaki disease，KD）临床表型的潜在相关性，以寻找中国儿童KD发生发展的高风险分子标记。方法采用病例对照研究，实验组包括238例KD患儿，对照组包含年龄与性别组成匹配的364名非KD儿童。同时应用聚合酶链式反应一限制性片段长度多态性与DNA测序技术，对研究对象的CASP3基因包括功能性单核苷酸多态位点（single nucleotide polymorphism，SNP）rs113420705在内的3个多态位点进行基因分型，分别比较KD组与对照组、继发与不继发冠状动脉损伤（coronary artery lesions，CALs）以及静脉注射免疫球蛋白（intravenous immunoglobulin，IVIG）治疗敏感与抗性情况下这些SNP位点等位基因与基因型频率。结果KD组中rs113420705的T等位基因频率与该等位基因携带者频率均显著高于对照组。在3种常见的单倍型中，2种包含SNPrs113420705风险等位基因的单倍型更常见于KD患者组。3个SNP位点的等位基因、基因型与次等位基因携带者频率在继发与不继发CALs患者组，以及IVIG治疗敏感与不敏感患者组之间差异均无统计学意义。结论cASP3基因rs113420705与中国人群川崎病的发生存在显著的相关性，提示该SNP的风险等位基因有希望成为判断中国儿童川崎病易患性的分子遗传标记。CASP3基因风险单倍型的证实为该基因在KD发生中的作用提供了新的证据。Objective The minor allele T of rs113420705 （C/T） in caspase-3 gene （CASP3）has been found to significantly increase the risk of Kawasaki disease （KD） and complicate coronary artery lesions （CALs） in Japanese children. In this study, we have explored association of single nucleotide polymorphisms （SNPs） of CASP3 gene and clinic phenotypes of KD. Methods A total of 238 unrelated KD patients and 364 healthy controls with matched age, gender and ethnic origins were recruited. Genotypes of the 3 SNPs were determined with PCR-restriction fragment length polymorphism （PCR-RFLP） and DNA sequencing. Allelic, genotypic and haplotypic frequencies were compared between patients and controls, patients with and without CALs, and patients resistant to and responsive to intravenous immunoglobulin （IVIG） treatment. Results The T allele and T carriers of rs113420705 were significantly more common in KD patients than controls. A significant difference was also detected in haplotype distribution between patients and controls, where two haplotypes involving the T allele of rs113420705 showed higher frequencies in the patient group. Allelic and genotypic frequencies of the 3 SNPs were similar between patients with and without CALs, and patients resistant to and responsive to IVIG treatment. Conclusion Our results suggested thatCASP3 probably plays an important role in KD. The T allele of rs113420705 may provide a useful marker for KD susceptibility, although no association between this SNP and clinical prognosis and treatment effect of KD has been found in the selected Chinese children patients.

关 键 词：川崎病 冠状动脉损伤 静脉滴注免疫球蛋白 半胱氨酸蛋白酶3基因 单核苷酸 多态性 

分 类 号：R725.4[医药卫生—儿科]