ADAM33基因及其血清水平与广西壮族儿童哮喘发病风险分析

doi:10.11852/zgetbjzz2022-0474

中国儿童保健杂志 ›› 2022, Vol. 30 ›› Issue (11): 1185-1190.DOI: 10.11852/zgetbjzz2022-0474

ADAM33基因及其血清水平与广西壮族儿童哮喘发病风险分析

杨丽娟^1,2, 邓高¹, 丁波³, 杨丽敏³, 李东明¹, 黄永方¹, 林娜¹

1.右江民族医学院附属医院儿科,广西百色 533000;
2.右江民族医学院研究生学院,广西百色 533000;
3.汉中三二0一医院

收稿日期:2022-04-18 修回日期:2022-05-31 发布日期:2022-11-09 出版日期:2022-11-10
通讯作者: 林娜, E-mail:linna7766328@163.com。
作者简介:杨丽娟,女,(1984-),云南人,主治医师,硕士研究生,研究方向为儿童呼吸系统疾病。
基金资助:
国家自然科学基金(81360003);广西高校中青年教师科研基础能力提升项目(桂教科研[2021]1 号)

Association of ADAM33 gene and its serum level with the risk of asthma in Zhuang children in Guangxi

YANG Li-juan^*, DENG Gao, DING Bo, YANG Li-min, LI Dong-ming, HUANG Yong-fang, LIN Na

^*Department of Pediatrics, the Affiliated Hospital of Youjiang Medical University for Nationalities,Baise,Guangxi 533000,China; Graduate School of Youjiang Medical University for Nationalities, Baise,Guangxi 533000,China

Received:2022-04-18 Revised:2022-05-31 Online:2022-11-10 Published:2022-11-09
Contact: LIN Na,E-mail:linna7766328@163.com

摘要/Abstract

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

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

中图分类号:

R725.6

杨丽娟, 邓高, 丁波, 杨丽敏, 李东明, 黄永方, 林娜. ADAM33基因及其血清水平与广西壮族儿童哮喘发病风险分析[J]. 中国儿童保健杂志, 2022, 30(11): 1185-1190.

YANG Li-juan, DENG Gao, DING Bo, YANG Li-min, LI Dong-ming, HUANG Yong-fang, LIN Na. Association of ADAM33 gene and its serum level with the risk of asthma in Zhuang children in Guangxi[J]. Chinese Journal of Child Health Care, 2022, 30(11): 1185-1190.

参考文献

[1] 王宁,王立军,任筱郿,等.西安城区儿童哮喘患病特点调查研究[J].陕西医学杂志,2018,47(5):674-677.
[2] Davies ER, Denney L, Wandel M, et al. Regulation of ectodomain shedding of ADAM33 in vitro and in vivo[J]. Allergy Clin Immunol,2019,143(6): 2281-2284.
[3] 中华医学会儿科学分会呼吸学组,《中华儿科杂志》编辑委员会. 儿童支气管哮喘诊断与防治指南(2016年版)[C].//第二十次全国儿科中西医结合学术会议论文集. 2016:47-61.
[4] Pividori M, Schoettler N, Nicolae DL, et al. Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: Genome-wide and transcriptome-wide studies[J]. Lancet Respir Med, 2019,7(6):509-522.
[5] Vishweswaraiah S, Ramachandra NB, Jayaraj BS, et al. Haplotype analysis of ADAM33 polymorphisms in asthma: A pilot study[J]. Indian J Med Res, 2019,150(3): 272-281.
[6] Fang L, Wu J, Huang T, et al. TGF-beta1 stimulates epithelial-mesenchymal transition mediated by ADAM33[J]. Exp Ther Med, 2018,15(1):985-992.
[7] Davies ER, Kelly JF, Howarth PH, et al. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life[J]. JCI Insight, 2016,1(11):87632.
[8] Ruan Z, Shi Z, Zhang G,et al. Asthma susceptible genes in children: A meta-analysis[J]. Medicine (Baltimore), 2020,99(45):e23051.
[9] Li HF, Yan LP, Wang K, et al. Association between ADAM33 polymorphisms and asthma risk:A systematic review and meta-analysis[J]. Respir Res, 2019,20(1):38.
[10] Shalaby SM, Abdul-Maksoud RS, Abdelsalam SM, et al. ADAM33 and ADAM12 genetic polymorphisms and their expression in Egyptian children with asthma[J]. Ann Allergy Asthma Immunol, 2016,116(1):31-36.
[11] Thongngarm T, Jameekornrak A, Chaiyaratana N, et al. Effect of gene polymorphisms in ADAM33, TGFβ1, VEGFA, and PLAUR on asthma in Thai population[J]. Asian Pac J Allergy Immunol, 2022,40(1):39-46.
[12] Farjadian S, Moghtaderi M, Hoseini-Pouya BA,et al. ADAM33 gene polymorphisms in Southwestern Iranian patients with asthma[J]. Iran J Basic Med Sci, 2018,21(8):813-817.
[13] Yilihamu N, Wushouer Q, Arkin K, et al. Association of a disintegrin and metalloprotease 33 gene polymorphisms with asthma[J]. Mol Clin Oncol, 2014,2(6):1076-1080.
[14] Ning X, Zhang Y, Wu H, et al. Genetic association of ADAM33 polymorphisms with childhood asthma in Chinese Han population: A case-control study[J]. Medicine (Baltimore), 2019,98(42):17327.
[15] Fan JG, Wang ZA, Zhao HX. The ADAM33 S2 polymorphism is associated with susceptibility to pediatric asthma in the Chinese Han population[J]. Genet Test Mol Biomarkers, 2015,19(10):573-578.
[16] 吴大威,杨玉双,崔清志,等. 8-异前列腺素、ADAM33基因、超敏C反应蛋白在慢性阻塞性肺疾病患者血清中表达的意义[J]. 国际检验医学杂志, 2018, 39(14):1782-1785.
[17] 李闯,刘建萍,石金河,等. 哮喘患者血清IL-17A、IL-18、ADAM33及SIP变化与病情程度的关系[J]. 实验与检验医学, 2020,38(3):489-491,520.
[18] 方丽萍,陈敏,张方,等. 解整合素-金属蛋白酶33在不同严重程度哮喘患者血清中的表达水平及其与气道慢性炎症的关系[J]. 医学研究生学报, 2017,30(5):521-524.
[19] 刘德义,马胜喜,刘雨婷. 解整合素-金属蛋白酶33、1-磷酸鞘氨醇水平与哮喘患者肺功能的关系及其意义[J]. 中国现代医学杂志, 2019,29(21):100-103.

ADAM33基因及其血清水平与广西壮族儿童哮喘发病风险分析

Association of ADAM33 gene and its serum level with the risk of asthma in Zhuang children in Guangxi

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