目的 研究β2肾上腺素受体（β2-drenergic receptor，ADRB2）基因调控区rs11168070、rs17108803、rs2053044、rs12654778、rs11959427和rs2895795位点单核苷酸多态性（single nucleotide polymorphism，SNP）/单倍型与儿童哮喘的关系，从而进一步探索儿童哮喘的发病机制。 方法 前瞻性选取2016年10月至2020年10月就诊的哮喘儿童143例（哮喘组），其中轻度61例（轻度组），中重度82例（中重度组）；137例健康儿童作为对照组。采集两组儿童外周静脉血，应用SNaPshot SNP技术检测所有儿童ADRB2基因调控区rs11168070、rs17108803、rs2053044、rs12654778、rs11959427和rs2895795位点SNP并分析单倍型，比较哮喘组和对照组儿童ADRB2基因调控区6个位点SNP/单倍型与哮喘易感及病情程度的关系。 结果 哮喘组和对照组儿童ADRB2基因调控区6个位点存在多态性，其中rs2895795（-1429T/A）、rs2053044（-1023G/A）和rs12654778（-654G/A）位点基因型及等位基因频率分布差异有统计学意义（P<0.05）。ADRB2基因调控区6个位点SNP存在连锁不平衡，构成的单倍型TATGCT、TATGGC和AGTGCT与儿童哮喘易感相关，其中TATGCT和TATGGC是儿童哮喘的危险因素（分别OR=1.792、1.946，P<0.05），而AGTGCT是保护性因素（OR=0.523，P<0.05）。 结论 ADRB2基因调控区SNP/单倍型与儿童哮喘易感性相关，其构成的单倍型TATGCT和TATGGC是儿童哮喘的危险因素，AGTGCT是保护性因素。 引用格式:
Abstract
Objective To study the association of β2-drenergic receptor (ADRB2) regulatory region single nucleotides polymorphism (SNP)/haplotypes at rs11168070, rs17108803, rs2053044, rs12654778, rs11959427, and rs2895795 loci with childhood asthma. Methods A total of 143 children with asthma who attended the hospital from October 2016 to October 2020 were enrolled as the asthma group, among whom 61 children had mild symptoms (mild group) and 82 children had moderate-to-severe symptoms (moderate-to-severe group). A total of 137 healthy children were enrolled as the control group. Peripheral venous blood samples were collected from the two groups. The SNaPshot SNP technique was used to analyze the SNP and haplotypes of the ADRB2 regulatory region at rs11168070, rs17108803, rs2053044, rs12654778, rs11959427, and rs2895795 loci in all children. The asthma group and the control group were compared in terms of the association of ADRB2 regulatory region SNP and haplotypes at the above six loci with susceptibility to asthma and severity of asthma. Results Polymorphisms were observed in the ADRB2 regulation region at the above six loci in both the asthma group and the control group, with significant differences between the two groups in the distribution of genotype and allele frequencies at rs2895795 (-1429T /A), rs2053044(-1023G/A), and rs12654778 (-654G/A) loci (P<0.05). Linkage disequilibrium of SNP was observed at the six loci of the ADRB2 regulatory region.The haplotypes of TATGCT, TATGGC, and AGTGCT were associated with susceptibility to childhood asthma, among which TATGCT and TATGGC were risk factors for childhood asthma (OR=1.792 and 1.946 respectively, P<0.05), while AGTGCT was a protective factor (OR=0.523, P<0.05). Conclusions SNP/haplotype of the ADRB2 regulatory region is associated with the susceptibility to childhood asthma. The haplotypes of TATGCT and TATGGC formed by such SNP/haplotype are risk factors for childhood asthma, while AGTGCT is a protective factor.
关键词
哮喘 /
ADRB2基因 /
易感性 /
单核苷酸多态性 /
单倍型 /
儿童
Key words
Asthma /
ADRB2 gene /
Susceptibility /
Single nucleotide polymorphism /
Haplotype /
Child
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参考文献
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基金
沈阳市科学技术计划（20-205-4-062）；辽宁省自然科学基金指导计划（20180550936）。
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