细胞毒T淋巴细胞相关抗原4基因多态性与儿童变应性鼻炎合并哮喘易感性的关系研究

Relationship between cytotoxic T lymphocyte associated antigen 4 gene polymorphism and susceptibility of children with allergic rhinitis complicated with asthma

目的研究儿童变应性鼻炎(allergic rhinitis,AR)合并哮喘疾病易感性与细胞毒T淋巴细胞相关抗原4(CTLA-4)基因多态性的关系。方法选取2019年10月至2020年10月郑州大学附属儿童医院变应性鼻炎患儿255例(AR组),其中仅患变应性鼻炎患儿101例作为A组,儿童变应性鼻炎AR合并哮喘患者144例作为B组,通过体检后确认无鼻炎、哮喘及其他过敏性疾病的健康儿童156例作为观察组,分别采集不同组别患者的外周血标本提取DNA后实施病例对比分析。对CTLA-4基因的6个多态性点(Rs 4553808、Rs 35219727、Rs 231725、Rs 3087243、Rs 11571315、Rs 11571302)采用直接测序法和限制性片段长度多态性聚合酶链反应实现基因分型。结果A组、B组和观察组的性别等基本资料差异无统计学意义(P>0.05);不同组别的等位基因及基因型的分析结果均符合哈迪温伯格平衡;观察组与A组的基因型频率与个体等位基因分析表明,Rs 231725A等位基因频率及AA基因型明显下降(P=0.012,OR=0.582,95%CIO为0.312~0.853;P=0.018,OR=0.747,95%CIO为0.619~0.945)。观察组与B组的基因型频率与个体等位基因分析表明,Rs 3087243A等位基因频率及AA基因型明显升高(P=0.005,OR=1.895,95%CIO为1.184~2.976;P=0.003,OR=1.411,95%CIO为1.236~1.786),Rs 231725A等位基因频率及AA基因型明显增高(P=0.029,OR=0.948,95%CIO为1.055~3.592;P=0.001,OR=1.541,95%CIO为1.204~1.987)。结论儿童AR合并哮喘的易感性与Rs 231725和Rs 3087243位点单核苷酸多态性密切相关,与细胞毒T淋巴细胞相关抗原4(CTLA-4)基因多态性存在显著相关性。

Objective To investigate the relationship between cytotoxic T lymphocyte associated antigen 4(CTLA-4)gene polymorphism and susceptibility to asthma in children with allergic rhinitis(AR).Methods A total of 255 cases of pediatric allergic rhinitis AR group were selected in our hospital from Oct.2019 to Oct.2020,including 101 cases of pediatric allergic rhinitis AR patients as group A,144 cases of pediatric allergic rhinitis AR patients with asthma as group B,and 156 healthy children without rhinitis,asthma and other allergic diseases confirmed by physical examination were selected as the observation group.Peripheral blood samples of different groups of patients were collected for DNA extraction and case comparative analysis was performed.Genotyping of six polymorphic points(Rs4553808,Rs35219727,Rs231725,Rs3087243,Rs11571315,Rs11571302)of CTLA-4 gene was performed by direct sequencing and restriction fragment length polymorphism polymerase chain reaction.Results There was no significant difference in gender and other basic data between group A,B and observation group.The results of alleles and genotypes in different groups were consistent with Hardiweinberg balance.The genotype frequency and individual allele analysis of observation group and group A showed that the allele frequency of Rs231725 A and AA genotype were significantly decreased(P=0.012,OR=0.582,95%CIO was 0.312~0.853;P=0.018,OR=0.747,95%CIO was 0.619~0.945).Genotype frequency and individual allele analysis of observation group and B group showed that allele frequency of Rs3087243 A and AA genotype were significantly increased(P=0.005,OR=1.895,95%CIO was 1.184~2.976;P=0.003,OR=1.411,95%CIO was 1.236~1.786),Rs231725 A allele frequency and AA genotype were significantly increased(P=0.029,OR=0.948,95%CIO was 1.055~3.592;P=0.001,OR=1.541,95%CIO was 1.204~1.987).Conclusion The susceptibility of AR combined with asthma in children is closely correlated with Rs231725 and Rs3087243 SNPS,and is significantly correlated with ctLA-4 gene polymorphism.