Abstract: Objective To investigate the association of the gene polymorphism of ADAM33 gene rs597980, rs44707, rs2853209, rs3918396 and rs511898 with asthma in children of Zhuang nationality in Guangxi, so as to provide a better solution for the individualized treatment of bronchial asthma in the Zhuang population. Methods From January 2021 to June 2021, 93 children diagnosed with asthma in the Department of Pediatrics of the Affiliated Hospital of Youjiang Medical University for Nationalities and 94 healthy children who took physical examination in the Children's Health Department during the same period were selected as the study subjects. Gene polymorphism of ADAM33 gene rs597980, rs44707, rs2853209, rs3918396 and rs511898 were analyzed, and the serum expression levels of ADAM33 in the two groups were detected. Results 1) Both groups were consistent with Hardy-Weinberg genetic equilibrium. 2) Genetic model showed that the asthmatic effect of TT genotype at rs511898 locus was 2.977 times (OR=2.977, P=0.023) as great as that of CC genotype and 2.615 times (OR=2.615, P=0.035) as great as that of CT+CC genotype. In additive model, the asthmatic effect of TT genotype was 2.834 times (OR=2.834, P=0.031) as great as that of CC genotype, and the asthmatic effect of T allele was 1.869 times (OR=1.869, P=0.005) as great as that of C allele. 3) There was a strong linkage disequilibrium between rs597980 and rs2853209 (D'=0.96, r² =0.60). 4) Haplotype analysis showed that the frequency of GGTCC and GGACC haplotypes in control group was significantly higher than that in asthma group(P< 0.05), and the frequency of GGTCT haplotypes in asthma group was significantly higher than that in control group(P<0.05). 5) There was significant difference in serum ADAM33 expression level between the two groups (t=13.379, P< 0.05). The serum levels of CC, CT and TT genotypes at rs511898 were significantly different between the two groups (t=8.002, 10.364, 3.748, P<0.05). Conclusion TT genotype and T allele at rs511898 of ADAM33 gene may be a risk factor for asthma progression in Zhuang children in Guangxi. Haplotype GGTCT may be a risk haplotype for asthma in Zhuang children in Guangxi. Increasing serum ADAM33 level may lead to the onset of asthma.

Key words: Guangxi Zhuang children, bronchial asthma, serum disintegrin metalloproteinase 33, single nucleotide polymorphism, haplotype

摘要： 目的 探讨解整合素-金属蛋白酶33(ADAM33)基因多态性及其血清水平与广西壮族儿童哮喘发病的相关性,为壮族儿童哮喘的个体化治疗提供更完善的方案。方法 选取2021年1—6月右江民族医学院附属医院儿内科确诊为哮喘的患儿93例及同期在儿童保健科体检的94名健康儿童为研究对象,行ADAM33基因(rs597980、rs44707、rs2853209、rs3918396、rs511898位点)分型,并检测两组血清ADAM33表达水平。结果 1)两组研究对象均符合Hardy-Weinberg遗传平衡; 2)遗传模型显示,rs511898位点的TT 基因型的致哮喘效应是CC基因型的2.977倍(OR＝2.977,P＝0.023)、是CT+CC组合基因型的2.615倍(OR=2.615,P＝0.035),加性模型TT基因型的致哮喘效应是CC基因型的2.834倍(OR=2.834,P＝0.031),T等位基因的致哮喘效应是C等位基因的1.869倍(OR＝1.869,P＝0.005); 3) rs597980与rs2853209位点呈强连锁不平衡(D'=0.96,r² =0.60); 4)单倍型分析发现,GGTCC、GGACC单倍型在对照组中的频率显著高于哮喘组(P<0.05),GGTCT单倍型在哮喘组中的频率显著高于对照组(P<0.05); 5)两组血清ADAM33表达水平差异有统计学意义(t=13.379,P<0.05);rs511898位点CC、CT及TT基因型的血清水平在两组研究对象间差异均有统计学意义(t=8.002、10.364、3.748,P<0.05)。结论 ADAM33基因rs511898位点TT基因型及T等位基因可能是广西壮族儿童哮喘进展的一个风险因素。单倍型GGTCT可能是广西壮族儿童哮喘发生的危险性单倍型。血清ADAM33增高可能导致壮族儿童哮喘的发生。

关键词: 广西壮族儿童, 支气管哮喘, 血清解整合素-金属蛋白酶33, 单核苷酸多态性, 单倍型