济南市某医疗机构手足口病患儿<i>TLR</i>9和<i>TLR</i>7基因多态性分析

周娜; 吴涛; 陈珊; 钱蛟; 王洪波

doi:10.16835/j.cnki.1000-9817.2024366

济南市某医疗机构手足口病患儿TLR9和TLR7基因多态性分析

doi: 10.16835/j.cnki.1000-9817.2024366

周娜¹,
吴涛²,
陈珊¹,
钱蛟³,
王洪波^1, ,

1.
山东省济南市第二妇幼保健院检验科， 271100
2.
济南市第二妇幼保健院儿科
3.
济南市第二妇幼保健院肛肠科

基金项目:

济南市卫生健康委科技计划项目 2023-1-50

详细信息

作者简介:
周娜(1985-)，女，硕士，主管检验技师，主要从事检验医学和遗传学工作

通讯作者:
王洪波，E-mail：1969387308@qq.com

利益冲突声明 所有作者声明无利益冲突。
中图分类号: R179 R181.3⁺² R511 Q343.1
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- 被引次数: 0
出版历程
- 收稿日期: 2024-08-08
- 修回日期: 2024-09-24
- 网络出版日期: 2025-01-07
- 刊出日期: 2024-12-25

Analysis of TLR9 and TLR7 gene polymorphisms among children with hand-foot-mouth disease in a medical institution of Jinan

ZHOU Na¹,
WU Tao²,
CHEN Shan¹,
QIAN Jiao³,
WANG Hongbo^{1
, ,}

1.
Department of Clinical Laboratory, the Second Children & Women' s Healthcare of Jinan, Jinan (271100), Shandong Province, China

摘要

摘要: 目的分析2020—2023年济南市某医疗机构手足口病患儿Toll样受体(TLR)9、TLR7基因多态性与手足口病的关系，为手足口病的预防提供参考依据。方法收集2020—2023年济南市第二妇幼保健院儿童感染科收治的284例3~6岁患儿手足口病发病季节、临床表现、病原体分布等资料。采用χ²检验比较肠道病毒71(EV71)亚型与柯萨奇病毒A组16型(CA16)亚型的TLR9、TLR7基因型分布情况，采用Hardy Weinbery平衡检测样本群体代表性，使用Logistic回归分析评估TLR9、TLR7基因多态性与手足口病亚型的关系。结果 284例手足口病患儿发病至入院时间以>2~4 d居多(45.42%)，其次为≤2 d(44.72%)；发病季节以夏季居多(58.10%)；严重程度以轻症居多(69.72%)；临床表现以皮疹(100.00%)、发热(65.49%)居多；病原体以EV71居多(60.56%)。Hardy Weinberg平衡检验结果显示，群体代表性良好(P>0.05)。在加性遗传模型下采用Logistic回归，校正研究人群年龄、性别后，分析TLR9 rs187084位点与手足口病亚型的关系，结果发现，与无C等位基因携带者相比，每多携带1个C等位基因，出现CA16亚型手足口病的风险增加109%(OR=2.09，95%CI=1.13~3.27)；分析TLR7 rs3853839位点与手足口病亚型的关系发现，与无C等位基因携带者相比，每多携带1个C等位基因，出现EV71亚型手足口病的风险增加57%(OR=1.57，95%CI=1.10~2.11)(P值均 < 0.05)。结论 2020—2023年济南市某医疗机构手足口病患儿以轻症及EV71感染居多，TLR7 rs3853839位点多态性可能与患儿EV71感染有关，TLR9 rs187084位点多态性可能与CA16感染有关。
- 手足口病 /
- 基因 /
- 回归分析 /
- 儿童，学龄前
Abstract: Objective To analyze the relationship between Toll-like receptor (TLR) 9 and TLR7 gene polymorphisms among children with hand-foot-mouth disease in a medical institution of Jinan City from 2020 to 2023, so as to provide reference for prevention of hand-foot-mouth disease. Methods Data of 284 preschool children aged 3-6 with hand-foot-mouth disease, including the season pattern, clinical manifestations, pathogen distribution, were collected in department of pediatric infectious diseases of the Second Children & Women's Healthcare of Jinan from 2020 to 2023. The distribution conditions of TLR9 and TLR7 genotypes of enterovirus 71 (EV71) subtype and coxsackievirus A16 (CA16) subtype were compared by Chi-square test. Hardy Weinberg equilibrium test was used to characteristic sample population distribution, and Logistic regression analysis in the additive genetic model was adopted to evaluate the relationship between TLR9 and TLR7 gene polymorphisms with hand-foot-mouth disease subtype. Results The time to admission after symptom onset with hand-foot-mouth disease among 284 children was mostly >2-4 d (45.42%), followed by ≤2 d (44.72%). The season pattern was mostly in summer (58.10%). The severity was mostly mild (69.72%), and the main clinical manifestations were skin rash (100.00%) and fever (65.49%). The majority pathogen was EV71 (60.56%). Hardy Weinberg equilibrium test showed good population representation (P>0.05). Logistic regression analysis was applied to analyze the relationship between TLR9 rs187084 locus and hand-foot-mouth disease subtypes under the additive genetic model after adjusting for age and gender of the study population, and it was found that compared with those without C allele, each additional C allele increased the risk of CA16 subtype hand-foot-mouth disease by 109% (OR=2.09, 95%CI=1.13-3.27). Analysis of relationship between TLR7 rs3853839 locus and hand-foot-mouth disease subtype showed that compared with those without C allele, the risk of EV71 subtype hand-foot-mouth disease increased by 57% for each additional C allele (OR=1.57, 95%CI=1.10-2.11) (P < 0.05). Conclusions From 2020 to 2023, children with hand-foot-mouth disease in a medical institution of Jinan City is mostly mild and caused by EV71 infection. The polymorphism of rs3853839 locus of TLR7 may be related to EV71 infection in children with hand-foot-mouth disease, and the polymorphism of rs187084 locus of TLR9 may be related to CA16 infection.
- Hand, foot and mouth disease /
- Genes /
- Regression analysis /
- Child, preschool
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表 1 TLR9及TLR7 PCR扩增引物序列

Table 1. PCR amplification primer sequences of TLR9 and TLR7

基因位点	引物序列(5′-3′)	长度(bp)	内切酶
TLR9 rs352140	正向：CTTGGCTGTGGATGTTGTTG 反向：TCAATGGCTCCCAGTTCC	237	BstUⅠ
TLR9 rs187084	正向：CATTCATTCAGCCCTTCACTCAG 反向：TATGTCTCTGCTCCCATGTCAC	356	AflⅡ
TLR7 rs3853839	正向：TGGTTGCTGCTTCAGTGCTT 反向：TGTGTCTTTCTTTCTTACTGTTTCCCT	370	EXOI
TLR7 rs179019	正向：TCAGGAGAGCAGGAAATCCTTT 反向：GCATAGCTATTATCTGGCTACAATGG	309	MspI

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参考文献(19)

[1]	彭远军, 何为涛, 郑志刚, 等. 广西2014—2018年重症手足口病空间流行特征[J]. 中国热带医学, 2023, 23(5): 473-478. PENG Y J, HE W T, ZHENG Z G, et al. Spatial epidemiological analysis of severe hand, foot and mouth disease in Guangxi, 2014-2018[J]. China Trop Med, 2023, 23(5): 473-478. (in Chinese)
[2]	LEUNG A K C, LAM J M, BARANKIN B, et al. Hand, foot, and mouth disease: a narrative review[J]. Recent Adv Inflamm Allergy Drug Discov, 2022, 16(2): 77-95. doi: 10.2174/1570180820666221024095837
[3]	TIKUTE S, LAVANIA M. Hand, foot, and mouth disease (HFMD) in India: a review on clinical manifestations, molecular epidemiology, pathogenesis, and prevention[J]. Indian Dermatol Online J, 2023, 14(4): 475-481. doi: 10.4103/idoj.idoj_423_22
[4]	郑晨晨, 散琴, 王字卉. TLR9启动子区基因多态性与柯萨奇病毒A16感染手足口病患儿的相关性研究[J]. 中国实验诊断学, 2023, 27(12): 1445-1449. doi: 10.3969/j.issn.1007-4287.2023.12.014 ZHENG C C, SAN Q, WANG Z H, et al. Correlation between TLR9 promoter gene polymorphism and Coxsackie virus A16 infection in children with hand, foot and mouth disease[J]. Chin J Lab Diagn, 2023, 27(12): 1445-1449. (in Chinese) doi: 10.3969/j.issn.1007-4287.2023.12.014
[5]	ZHANG Y, SUO X, ZHANG Y. Association of IL-13, S100B, and TLR-7 gene polymorphisms with enterovirus 71 infection in hand, foot, and mouth disease in China[J]. Genet Test Mol Biomarkers, 2019, 23(3): 188-196. doi: 10.1089/gtmb.2018.0239
[6]	《手足口病诊疗指南(2018版)》编写专家委员会. 手足口病诊疗指南(2018年版)[J]. 中华传染病杂志, 2018, 36(5): 257-263. Expert Committee for Guidelines for the Diagnosis and Treatment of Hand, Foot, and Mouth Disease. Guidelines for the diagnosis and treatment of hand, foot, and mouth disease (2018 Edition)[J]. Chin J Infect Dis, 2018, 36(5): 257-263. (in Chinese)
[7]	梁兆毅, 孟君, 张艳炜, 等. 深圳市2008-2020年手足口病流行特征及EV71疫苗接种对其发病率影响[J]. 中国公共卫生, 2023, 39(2): 249-252. LIANG Z Y, MENG J, ZHANG Y W, et al. Epidemiological characteristics of hand, foot and mouth disease in Shenzhen from 2008 to 2020 and effect of inactivated EV71 vaccine on disease incidence[J]. Chin J Public Health, 2023, 39(2): 249-252. (in Chinese)
[8]	马婉婉, 龚磊, 肖永康, 等. 2015—2022年安徽省手足口病流行病学特征及病原谱变化[J]. 安徽医科大学学报, 2023, 58(10): 1763-1768. MA W W, GONG L, XIAO Y K, et al. Epidemiological characteristics and pathogen spectrum changes of hand-foot-mouth disease in Anhui Province from 2015 to 2022[J]. Acta Univ Med Anhui, 2023, 58(10): 1763-1768. (in Chinese)
[9]	SHOUKAT M, ULLAH R, JAVAID M, et al. TLR-2 germ line variants as a risk for obesity in local pakistani population[J]. Arch Med Res, 2022, 53(4): 359-367. doi: 10.1016/j.arcmed.2022.04.006
[10]	YANG R, YAO T, XU J, et al. Peptide-TLR7/8a-coordinated DNA vaccines elicit enhanced immune responses against infectious diseases[J]. ACS Biomater Sci Eng, 2024, 10(7): 4374-4387. doi: 10.1021/acsbiomaterials.4c00749
[11]	EL-HEFNAWY S M, EID H A, MOSTAFA R G, et al. COVID-19 susceptibility, severity, clinical outcome and Toll-like receptor (7) mRNA expression driven by TLR7 gene polymorphism (rs3853839) in middle-aged individuals without previous comorbidities[J]. Gene Rep, 2022, 27(1): e101612.
[12]	RANJAN S, PANDA A K. Association of Toll-like receptor 7 (TLR7) polymorphisms with predisposition to systemic lupus erythematosus (SLE): a Meta and trial sequential analysis[J]. Biochem Genet, 2023, 16(1): 1-10.
[13]	TIAN H, XU W, WEN L, et al. Association of TLR3 gene 1377C/T (rs3775290) and TLR7 gene C/G (rs3853839) polymorphism with hand, foot, and mouth disease caused by human enterovirus 71 infection susceptibility and severity in the Chinese Han population: a Meta-analysis of case-control studies[J]. Medicine (Baltimore), 2022, 101(27): e29758. doi: 10.1097/MD.0000000000029758
[14]	CHEN G P, XIANG K, SUN L, et al. TLR3 polymorphisms are associated with the severity of hand, foot, and mouth disease caused by enterovirus A71 in a Chinese children population[J]. J Med Virol, 2021, 93(11): 6172-6179. doi: 10.1002/jmv.27115
[15]	MANDAL A, KUMAR M, KUMAR A, et al. TLR4 and TLR9 polymorphism: probable role in susceptibility among the population of Bihar for Indian visceral leishmaniasis[J]. Innate Immun, 2021, 27(6): 493-500. doi: 10.1177/1753425920965658
[16]	KULMANN-LEAL B, ELLWANGER J H, VALVERDE-VILLEGAS J M, et al. TLR9 2848 G/A gene polymorphism in HCV+, HIV+, and HCV+/HIV+ individuals[J]. Genet Test Mol Biomarkers, 2022, 26(5): 263-269. doi: 10.1089/gtmb.2021.0288
[17]	TADAYON Z, SHAHZADEH FAZELI S A, GHOLIJANI N, et al. Toll-like receptor 9 (TLR9) genetic variants rs187084 and rs352140 confer protection from Behcet's disease among Iranians[J]. BMC Rheumatol, 2024, 8(1): 1-13. doi: 10.1186/s41927-023-00370-7
[18]	罗筱, 白宝鑫, 王爽. CoxA16感染儿童手足口病患者IL-6、IFN-α水平变化及其与TLR9基因多态性的相关性[J]. 重庆医学, 2023, 52(17): 2597-2601, 2605. LUO X, BAI B X, WANG S. Changes of IL-6 and IFN-α levels in children with hand, foot and mouth disease infected by CoxA16 and their correlation with TLR9 gene polymorphism[J]. Chongqing Med, 2023, 52(17): 2597-2601, 2605. (in Chinese)
[19]	LAI R H, CHOW Y H, CHUNG N H, et al. Neurotropic EV71 causes encephalitis by engaging intracellular TLR9 to elicit neurotoxic IL12-p40-iNOS signaling[J]. Cell Death Dis, 2022, 13(4): 328-330.