<italic>MTHFR</italic>基因多态性与儿童支气管哮喘易感性及糖皮质激素疗效的相关性

doi:10.7499/j.issn.1008-8830.2105035

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Abstract Objective To study the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with susceptibility to bronchial asthma and glucocorticoid (GC) efficacy in children. Methods A total of 173 children with bronchial asthma who were hospitalized between June 2018 and December 2020 were selected as the observation group. The children received aerosol inhalation of GC for three consecutive months. A total of 178 healthy children who underwent physical examination during the same period were selected as the control group. PCR was used to detect the genotypes of the MTHFR C677T for the two groups. The differences in genotype distribution between the two groups were analyzed. Children with different genotypes in the observation group were compared in terms of immunoglobulin E (IgE), interleukin-8 (IL-8), leukotriene B4 (LTB4), lung function, and clinical outcome before and after treatment. Results TT genotype and T allele were significantly more frequent in the observation group than in the control group (P<0.001). TT/CT genotypes and T allele were independent risk factors for bronchial asthma (OR=6.615 and 7.055 respectively; P<0.001). After GC treatment, the children with CC, CT or TT genotypes experienced significantly decreased levels of IgE, IL-8, and LTB4 and significantly increased forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio (P<0.001). The children with TT genotype showed significantly lower levels of IL-8 and LTB4 than those with CC genotype, a significantly lower level of LTB4 than those with CT genotype, significantly higher FVC than those with CT genotype, and a significantly higher FEV1/FVC ratio than those with CC genotype (P<0.05). The children with TT genotype had better GC efficacy compared with those with CC genotype (P<0.05). TT genotype was an independent factor for good GC efficacy (OR=2.111, P=0.018). Conclusions MTHFR gene polymorphism is associated with asthma susceptibility and GC efficacy in children. Children carrying TT/CT genotypes have a higher risk of developing asthma, and those with TT genotype are more sensitive to GC treatment.

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	LI Min
	TANG Yu
	ZHAO Er-Yao
	CHEN Chao-Hui
	DONG Li-Li

Key words： Bronchial asthma Methylenetetrahydrofolate reductase Gene polymorphism Glucocorticoid Child

Received: 11 May 2021

Corresponding Authors: Tang Y, Email: httang0@163.com E-mail: httang0@163.com

Cite this article:

LI Min,TANG Yu,ZHAO Er-Yao et al. Relationship between MTHFR gene polymorphism and susceptibility to bronchial asthma and glucocorticoid efficacy in children[J]. CJCP, 2021, 23(8): 802-808.

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http://www.zgddek.com/EN/10.7499/j.issn.1008-8830.2105035 OR http://www.zgddek.com/EN/Y2021/V23/I8/802

	1 顾秋千, 徐萍芳. 儿童支气管哮喘流行病学特点与研究现状[J]. 健康大视野, 2020(12): 246-247.
	2 洪建国. 我国儿童哮喘流行病学和诊治状况[J]. 中华医学信息导报, 2020, 35(2): 22. DOI: 10.3760/cma.j.issn.1000-8039.2020.02.133.
	Slob EM, Maitland-Van der Zee AH, Koppelman GH, et al. Precision medicine in childhood asthma[J]. Curr Opin Allergy Clin Immunol, 2019, 19(2): 141-147. DOI: 10.1097/ACI.0000000000000517. PMID: 30649013.
	4 李剑雄, 邱玉明, 李慧. 哮喘患者FCER2基因T2206 C位点多态性与吸入糖皮质激素治疗反应的相关性[J]. 广东医学, 2017, 38(19): 2969-2971. DOI: 10.3969/j.issn.1001-9448.2017.19.016.
	Sun CG, Yue WJ, Yan XL, et al. Correlation of SOCS3 gene polymorphism with childhood asthma[J]. Eur Rev Med Pharmacol Sci, 2019, 23(17): 7563-7567. DOI: 10.26355/eurrev_201909_18876. PMID: 31539147.
	6 朱慧萍, 刘明珠, 刀京晶, 等. MTHFR基因第1298位核苷酸多态性与酶活性的关系[J]. 北京医科大学学报, 2000, 32(3): 262-264. DOI: 10.3321/j.issn:1671-167X.2000.03.019.
	7 孙淑媛, 杨丽萍, 路旭红, 等. 亚甲基四氢叶酸还原酶基因多态性及血浆半胱氨酸水平与儿童支气管哮喘的关系研究[J]. 广西医学, 2013, 35(11): 1499-1501. DOI: 10.11675/j.issn.0253-4304.2013.11.23.
	8 边艳琴, 孙阳, 季蔚青, 等. 甲氨蝶呤、来氟米特药物相关基因多态性在类风湿关节炎患者中的基因型分布[J]. 中华风湿病学杂志, 2020, 24(4): 226-233. DOI: 10.3760/cma.j.cn141217-20190618-00227.
	中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南(2020年版)[J]. 中华结核和呼吸杂志, 2020, 43(12): 1023-1048. DOI: 10.3760/cma.j.cn112147-20200618-00721. PMID: 33333637.
	10 中华医学会儿科学分会呼吸学组, 中华医学会《中华儿科杂志》编辑委员会. 儿童支气管哮喘防治常规(试行)(附件: 哮喘常用药物及治疗简介)[J]. 中华儿科杂志, 2004, 42(2): 100-106. DOI: 10.3760/j.issn:0578-1310.2004.02.007.
	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)[J]. 中华儿科杂志, 2016, 54(3): 167-181. DOI: 10.3760/cma.j.issn.0578-1310.2016.03.003. PMID: 26957061.
	Kogan V, Millstein J, London SJ, et al. Genetic-epigenetic interactions in asthma revealed by a genome-wide gene-centric search[J]. Hum Hered, 2018, 83(3): 130-152. DOI: 10.1159/000489765. PMID: 30669148. PMCID: PMC7365350.
	Alghobashy AA, Elsharawy SA, Alkholy UM, et al. B2 adrenergic receptor gene polymorphism effect on childhood asthma severity and response to treatment[J]. Pediatr Res, 2018, 83(3): 597-605. DOI: 10.1038/pr.2017.304. PMID: 29658513.
	Cao JH, Tian LJ, Li ZG, et al. Interleukin-7 gene polymorphism rs766736182 associates with the risk of asthma in children[J]. J Clin Lab Anal, 2019, 33(2): e22675. DOI: 10.1002/jcla.22675. PMID: 30239047. PMCID: PMC6818573.
	Imani D, Eslami MM, Anani-Sarab G, et al. Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications[J]. BMC Med Genet, 2020, 21(1): 232. DOI: 10.1186/s12881-020-01169-w. PMID: 33228581. PMCID: PMC7686752.
	Wan L, Li YH, Zhang ZR, et al. Methylenetetrahydrofolate reductase and psychiatric diseases[J]. Transl Psychiatry, 2018, 8(1): 242. DOI: 10.1038/s41398-018-0276-6. PMID: 30397195. PMCID: PMC6218441.
	Sookaromdee P, Wiwanitkit V. MTHFR C677T polymorphism and hypertension[J]. J Clin Hypertens (Greenwich), 2020, 22(2): 308. DOI: 10.1111/jch.13811. PMID: 31955498.
	Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases[J]. Eur J Med Genet, 2015, 58(1): 1-10. DOI: 10.1016/j.ejmg.2014.10.004. PMID: 25449138.
	Zeng H, He DM, Zhao YH, et al. Association between MTHFR polymorphisms (MTHFR C677T, MTHFR A1298C) and recurrent implantation failure: a systematic review and meta-analysis[J]. Arch Gynecol Obstet, 2021, 303(4): 1089-1098. DOI: 10.1007/s00404-020-05851-5. PMID: 33128585.
	Han IB, Kim OJ, Ahn JY, et al. Association of methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) polymorphisms and haplotypes with silent brain infarction and homocysteine levels in a Korean population[J]. Yonsei Med J, 2010, 51(2): 253-260. DOI: 10.3349/ymj.2010.51.2.253. PMID: 20191019. PMCID: PMC2824873.
	Ventura P, Venturelli G, Marcacci M, et al. Hyperhomocysteinemia and MTHFR C677T polymorphism in patients with portal vein thrombosis complicating liver cirrhosis[J]. Thromb Res, 2016, 141: 189-195. DOI: 10.1016/j.thromres.2016.03.024. PMID: 27065203.
	22 曹庆阳, 高宇, 宁志杰, 等. 缺血性青年脑卒中脑动脉狭窄与血浆HCY水平及MTHFR C677T基因多态性的相关性研究[J]. 中风与神经疾病杂志, 2020, 37(3): 237-241. DOI: 10.19845/j.cnki.zfysjjbzz.2020.0311.
	23 陈文举, 王攀, 钟倩怡, 等. MTHFR基因多态性与台州地区儿童哮喘的相关性研究[J]. 中国卫生检验杂志, 2020, 30(9): 1095-1097.
	24 彭昊, 龙博文, 钟炜, 等. 支气管哮喘患儿CHI3L1基因多态性与糖皮质激素疗效的关系研究[J]. 中国现代医学杂志, 2021, 31(3): 24-30. DOI: 10.3969/j.issn.1005-8982.2021.03.005.
	25 熊晓琦, 宋新宇, 曾凡军, 等. 支气管哮喘患者eotaxin-3基因多态性对吸入糖皮质激素的影响[J]. 重庆医学, 2017, 46(27): 3786-3788. DOI: 10.3969/j.issn.1671-8348.2017.27.013.
	Mohamed NA, Abdel-Rehim AS. Influence of vitamin D receptor gene FokI and ApaI polymorphisms on glucocorticoid response in patients with asthma[J]. Int Forum Allergy Rhinol, 2020, 10(4): 556-563. DOI: 10.1002/alr.22511. PMID: 31863554.
	Zein J, Gaston B, Bazeley P, et al. HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma[J]. Proc Natl Acad Sci U S A, 2020, 117(4): 2187-2193. DOI: 10.1073/pnas.1918819117. PMID: 31932420. PMCID: PMC6995013.
	Shiobara T, Chibana K, Watanabe T, et al. Dipeptidyl peptidase-4 is highly expressed in bronchial epithelial cells of untreated asthma and it increases cell proliferation along with fibronectin production in airway constitutive cells[J]. Respir Res, 2016, 17: 28. DOI: 10.1186/s12931-016-0342-7. PMID: 26975422. PMCID: PMC4791890.
	Ma K, Lu N, Zou F, et al. Sirtuins as novel targets in the pathogenesis of airway inflammation in bronchial asthma[J]. Eur J Pharmacol, 2019, 865: 172670. DOI: 10.1016/j.ejphar.2019.172670. PMID: 31542484.
	de Benedictis FM, Attanasi M. Asthma in childhood[J]. Eur Respir Rev, 2016, 25(139): 41-47. DOI: 10.1183/16000617.0082-2015. PMID: 26929420.