水痘患者toll样受体基因多态性:观察队列研究

T. A. Krivolutskaya, A. N. Emelyanova, A. Emelyanov, Y. Vitkovsky
{"title":"水痘患者toll样受体基因多态性:观察队列研究","authors":"T. A. Krivolutskaya, A. N. Emelyanova, A. Emelyanov, Y. Vitkovsky","doi":"10.25207/1608-6228-2022-29-5-14-28","DOIUrl":null,"url":null,"abstract":"Background. Toll-like receptors (TLR) play a key role in the innate immune system, as they are the fi rst to recognize a foreign agent and initiate the human body defense mechanism. At present, the role of toll-like receptors in predicting infectious diseases requires further investigation.Objectives. To study TLR3 (Phe412Leu), TLR9 (A2848G) and TLR9 (T1237C) polymorphisms in healthy individuals and chickenpox patientsMethods. An observational cohort study involved 201 conscripted soldiers of Caucasian race, aged between 18 and 24, who was born in) and served in Zabaykalsky Krai. All of them agreed to participate voluntarily. The main group was represented by 105 males who received treatment at a military hospital with a diagnosis of chickenpox in 2019. The control group consisted of 96 healthy conscripts. The study was carried out on the basis of Chita State Academy of Medicine, Russia, and included a physical examination, anthropometry, determination of SNP genes by PCR. Amplifi cation of TLR3 and TLR9 gene fragments was carried out by means of thermocycler BIS-М111. IBM SPSS Statistics 25.0 (International Business Machines Corporation, License No. Z125-3301-14, USA) was used for statistical processing of the results.Results. A total of 354 people were screened, 87 of them did not meet the inclusion criteria and 19 refused to participate in the study. 134 males were excluded in the process, 47 of which appeared to have an exacerbation of chronic diseases, 21 were not of Caucasian race, 64 were not born in Zabaykalsky Krai, and 2 did not meet the age criteria. Totally, the study included 201 conscripted soldiers. The study groups were established as follows: chickenpox patients (n = 105) and healthy individuals (controls, n = 96). The -412Leu allele was 1.8 times less frequent in the chickenpox group, with a frequency of 0.138, compared with 0.250 in healthy controls (Ȥ 2 = 8.11; p = 0.004). In the main group, allele -412Phe prevailed with a frequency of 0.862, whereas in the control group its frequency was 0.750 (χ2 = 8.11; p = 0.004). In patients group, the genoype Phe412Phe prevailed (75.2%), the genotype Leu412Leu was less common — 2.9% (Ȥ 2 = 7.09; p = 0.03). In the group of healthy individuals, the distribution of genotypes was as follows: Phe412Phe — 60.4%, Phe412Leu — 30.2%, Leu412Leu — 9.4% (Ȥ 2 = 7.09; ɪ = 0.03). Carriers of allele -412Phe (OR = 2.08 [CI95%: 1.25–3.47]) and genotype Phe412Phe (OR = 2.08 [CI95%: 1.14–3.80]) are more likely to develop chickenpox. The probability of developing the disease for persons having the major allele A of the genotype TLR9 (Ⱥ2848G) is 0.29 [CI95%: 0.19– 0.43], for individuals with the mutant allele G of the genotype TLR9 (Ⱥ2848G) — 3.50 [CI95%: 2.32–5.29]. The prevalence of TLR9 (T1237C) in the main group was not signifi cantly different from that in the control group (p > 0.05). The probability of developing the disease for persons having the major allele A is 0.29 [95% CI 0.19–0.43], for carriers of the mutant allele G — 3.50 [95% CI 2.32-5.29]. When analyzing SNP TLR9 (A2848G), it was found that allele G prevailed with a frequency of 0.614, and allele A — with a frequency of 0.386, which is 1.9 times less than in the control group (Ȥ 2 = 36.67; p < 0.001). In patients group, homozygotes AA were found in 9.5% of cases, heterozygotes AG — in 58.1%, the rest cases were homozygous variants GG (Ȥ 2 = 40.11; p < 0.001). In the control group, all possible genotypes with a predominance of the heterozygous genotype AG were identifi ed and comprised 47.9%. When assessing the relative risk of gene variation associations connected with the development of chickenpox, we found that the polymorphism of genes TLR9 (A2848G) AG/GG increases the risk of the development of disease caused by varicella virus in the studied category by 3.4 times, and the polymorphism TLR3 (Phe412Leu) Phe/ Phe — by 1.42 times. The ROC analysis was carried out, the area under curve was 0.77 (95% CI0.70–0.83); p < 0.001; specifi city — 0.62; sensitivity — 0.8. The developed model, being a relatively good identifi er, has satisfactory properties as a discriminator.Conclusion. Our study suggests that allele -412Phe and homozygous variant Phe412Phe of gene TLR3 (Phe412Leu), as well as allele G and homozygous variant GG of gene TLR9 (A2848G) predispose to chickenpox development. Meanwhile, the allele -412Leu of gene TLR3 (Phe412Leu), allele A, and homozygous variant AA of gene TLR9 (A2848G) reduce the probability of chickenpox development.","PeriodicalId":33483,"journal":{"name":"Kubanskii nauchnyi meditsinskii vestnik","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Gene Polymorphism of Toll-Like Receptors in Chickenpox Patients: Observational Cohort Study\",\"authors\":\"T. A. Krivolutskaya, A. N. Emelyanova, A. Emelyanov, Y. Vitkovsky\",\"doi\":\"10.25207/1608-6228-2022-29-5-14-28\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background. Toll-like receptors (TLR) play a key role in the innate immune system, as they are the fi rst to recognize a foreign agent and initiate the human body defense mechanism. At present, the role of toll-like receptors in predicting infectious diseases requires further investigation.Objectives. To study TLR3 (Phe412Leu), TLR9 (A2848G) and TLR9 (T1237C) polymorphisms in healthy individuals and chickenpox patientsMethods. An observational cohort study involved 201 conscripted soldiers of Caucasian race, aged between 18 and 24, who was born in) and served in Zabaykalsky Krai. All of them agreed to participate voluntarily. The main group was represented by 105 males who received treatment at a military hospital with a diagnosis of chickenpox in 2019. The control group consisted of 96 healthy conscripts. The study was carried out on the basis of Chita State Academy of Medicine, Russia, and included a physical examination, anthropometry, determination of SNP genes by PCR. Amplifi cation of TLR3 and TLR9 gene fragments was carried out by means of thermocycler BIS-М111. IBM SPSS Statistics 25.0 (International Business Machines Corporation, License No. Z125-3301-14, USA) was used for statistical processing of the results.Results. A total of 354 people were screened, 87 of them did not meet the inclusion criteria and 19 refused to participate in the study. 134 males were excluded in the process, 47 of which appeared to have an exacerbation of chronic diseases, 21 were not of Caucasian race, 64 were not born in Zabaykalsky Krai, and 2 did not meet the age criteria. Totally, the study included 201 conscripted soldiers. The study groups were established as follows: chickenpox patients (n = 105) and healthy individuals (controls, n = 96). The -412Leu allele was 1.8 times less frequent in the chickenpox group, with a frequency of 0.138, compared with 0.250 in healthy controls (Ȥ 2 = 8.11; p = 0.004). In the main group, allele -412Phe prevailed with a frequency of 0.862, whereas in the control group its frequency was 0.750 (χ2 = 8.11; p = 0.004). In patients group, the genoype Phe412Phe prevailed (75.2%), the genotype Leu412Leu was less common — 2.9% (Ȥ 2 = 7.09; p = 0.03). In the group of healthy individuals, the distribution of genotypes was as follows: Phe412Phe — 60.4%, Phe412Leu — 30.2%, Leu412Leu — 9.4% (Ȥ 2 = 7.09; ɪ = 0.03). Carriers of allele -412Phe (OR = 2.08 [CI95%: 1.25–3.47]) and genotype Phe412Phe (OR = 2.08 [CI95%: 1.14–3.80]) are more likely to develop chickenpox. The probability of developing the disease for persons having the major allele A of the genotype TLR9 (Ⱥ2848G) is 0.29 [CI95%: 0.19– 0.43], for individuals with the mutant allele G of the genotype TLR9 (Ⱥ2848G) — 3.50 [CI95%: 2.32–5.29]. The prevalence of TLR9 (T1237C) in the main group was not signifi cantly different from that in the control group (p > 0.05). The probability of developing the disease for persons having the major allele A is 0.29 [95% CI 0.19–0.43], for carriers of the mutant allele G — 3.50 [95% CI 2.32-5.29]. When analyzing SNP TLR9 (A2848G), it was found that allele G prevailed with a frequency of 0.614, and allele A — with a frequency of 0.386, which is 1.9 times less than in the control group (Ȥ 2 = 36.67; p < 0.001). In patients group, homozygotes AA were found in 9.5% of cases, heterozygotes AG — in 58.1%, the rest cases were homozygous variants GG (Ȥ 2 = 40.11; p < 0.001). In the control group, all possible genotypes with a predominance of the heterozygous genotype AG were identifi ed and comprised 47.9%. When assessing the relative risk of gene variation associations connected with the development of chickenpox, we found that the polymorphism of genes TLR9 (A2848G) AG/GG increases the risk of the development of disease caused by varicella virus in the studied category by 3.4 times, and the polymorphism TLR3 (Phe412Leu) Phe/ Phe — by 1.42 times. The ROC analysis was carried out, the area under curve was 0.77 (95% CI0.70–0.83); p < 0.001; specifi city — 0.62; sensitivity — 0.8. The developed model, being a relatively good identifi er, has satisfactory properties as a discriminator.Conclusion. Our study suggests that allele -412Phe and homozygous variant Phe412Phe of gene TLR3 (Phe412Leu), as well as allele G and homozygous variant GG of gene TLR9 (A2848G) predispose to chickenpox development. Meanwhile, the allele -412Leu of gene TLR3 (Phe412Leu), allele A, and homozygous variant AA of gene TLR9 (A2848G) reduce the probability of chickenpox development.\",\"PeriodicalId\":33483,\"journal\":{\"name\":\"Kubanskii nauchnyi meditsinskii vestnik\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kubanskii nauchnyi meditsinskii vestnik\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.25207/1608-6228-2022-29-5-14-28\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kubanskii nauchnyi meditsinskii vestnik","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.25207/1608-6228-2022-29-5-14-28","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

背景。toll样受体(TLR)在先天免疫系统中起着关键作用,因为它们是第一个识别外来物并启动人体防御机制的细胞。目前,toll样受体在预测传染病中的作用有待进一步研究。研究健康人群和水痘患者TLR3 (Phe412Leu)、TLR9 (A2848G)和TLR9 (T1237C)基因多态性。一项观察性队列研究涉及201名年龄在18至24岁之间的白种人士兵,他们出生在),并在扎巴卡尔斯基边疆区服役。他们都同意自愿参加。主要人群为105名男性,他们在2019年被诊断为水痘,在军队医院接受了治疗。对照组为96名健康应征入伍者。该研究以俄罗斯赤塔国立医学院为基础进行,包括体格检查、人体测量、PCR检测SNP基因。利用热循环仪BIS-М111扩增TLR3和TLR9基因片段。IBM SPSS Statistics 25.0(国际商业机器公司,许可证号:采用Z125-3301-14,美国)对结果进行统计处理。共筛选了354人,其中87人不符合纳入标准,19人拒绝参与研究。134名男性在这一过程中被排除在外,其中47人似乎有慢性疾病加重,21人不是高加索人,64人不是在扎贝卡尔斯基边疆区出生,2人不符合年龄标准。这项研究总共包括201名应征入伍的士兵。研究分组如下:水痘患者(n = 105)和健康个体(n = 96)。-412Leu等位基因在水痘组的频率为0.138,比健康对照组的0.250低1.8倍(Ȥ 2 = 8.11;P = 0.004)。主组-412Phe等位基因患病率为0.862,对照组患病率为0.750,差异有统计学意义(χ2 = 8.11;P = 0.004)。患者组以Phe412Phe基因型居多(75.2%),Leu412Leu基因型较少(2.9%)(Ȥ 2 = 7.09;P = 0.03)。健康人群中基因型分布为:Phe412Phe - 60.4%, Phe412Leu - 30.2%, Leu412Leu - 9.4% (Ȥ 2 = 7.09;/ = 0.03)。携带等位基因-412Phe (OR = 2.08 [CI95%: 1.25-3.47])和基因型Phe412Phe (OR = 2.08 [CI95%: 1.14-3.80])的人更容易患水痘。携带TLR9基因型主要等位基因A (Ⱥ2848G)的人患该病的概率为0.29 [CI95%: 0.19 - 0.43],携带TLR9基因型突变等位基因G (Ⱥ2848G)的人患该病的概率为3.50 [CI95%: 2.32-5.29]。主组TLR9 (T1237C)阳性率与对照组比较差异无统计学意义(p < 0.05)。携带主要等位基因A的人患该病的概率为0.29 [95% CI 0.19-0.43],携带突变等位基因G -的人患该病的概率为3.50 [95% CI 2.32-5.29]。在分析SNP TLR9 (A2848G)时,发现等位基因G的频率为0.614,等位基因a -的频率为0.386,比对照组低1.9倍(Ȥ 2 = 36.67;P < 0.001)。患者组纯合子AA占9.5%,杂合子AG -占58.1%,纯合子GG占58.1% (Ȥ 2 = 40.11;P < 0.001)。在对照组中,所有可能的基因型均以AG杂合基因型为优势,占47.9%。在评估水痘发病相关基因变异的相对风险时,我们发现基因TLR9 (A2848G) AG/GG多态性使研究类别水痘病毒发病风险增加3.4倍,基因TLR3 (Phe412Leu) Phe/ Phe -多态性使研究类别水痘病毒发病风险增加1.42倍。进行ROC分析,曲线下面积为0.77 (95% CI0.70-0.83);P < 0.001;特异性城市- 0.62;灵敏度- 0.8。所建立的模型具有良好的判别性能,是一种较好的判别器。我们的研究表明,基因TLR3 (Phe412Leu)的等位基因-412Phe和纯合变异体Phe412Phe,以及基因TLR9 (A2848G)的等位基因G和纯合变异体GG易导致水痘的发生。同时,TLR3基因的等位基因-412Leu (Phe412Leu)、TLR9基因的等位基因A、TLR9基因的纯合变异体AA (A2848G)降低了水痘发生的几率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Gene Polymorphism of Toll-Like Receptors in Chickenpox Patients: Observational Cohort Study
Background. Toll-like receptors (TLR) play a key role in the innate immune system, as they are the fi rst to recognize a foreign agent and initiate the human body defense mechanism. At present, the role of toll-like receptors in predicting infectious diseases requires further investigation.Objectives. To study TLR3 (Phe412Leu), TLR9 (A2848G) and TLR9 (T1237C) polymorphisms in healthy individuals and chickenpox patientsMethods. An observational cohort study involved 201 conscripted soldiers of Caucasian race, aged between 18 and 24, who was born in) and served in Zabaykalsky Krai. All of them agreed to participate voluntarily. The main group was represented by 105 males who received treatment at a military hospital with a diagnosis of chickenpox in 2019. The control group consisted of 96 healthy conscripts. The study was carried out on the basis of Chita State Academy of Medicine, Russia, and included a physical examination, anthropometry, determination of SNP genes by PCR. Amplifi cation of TLR3 and TLR9 gene fragments was carried out by means of thermocycler BIS-М111. IBM SPSS Statistics 25.0 (International Business Machines Corporation, License No. Z125-3301-14, USA) was used for statistical processing of the results.Results. A total of 354 people were screened, 87 of them did not meet the inclusion criteria and 19 refused to participate in the study. 134 males were excluded in the process, 47 of which appeared to have an exacerbation of chronic diseases, 21 were not of Caucasian race, 64 were not born in Zabaykalsky Krai, and 2 did not meet the age criteria. Totally, the study included 201 conscripted soldiers. The study groups were established as follows: chickenpox patients (n = 105) and healthy individuals (controls, n = 96). The -412Leu allele was 1.8 times less frequent in the chickenpox group, with a frequency of 0.138, compared with 0.250 in healthy controls (Ȥ 2 = 8.11; p = 0.004). In the main group, allele -412Phe prevailed with a frequency of 0.862, whereas in the control group its frequency was 0.750 (χ2 = 8.11; p = 0.004). In patients group, the genoype Phe412Phe prevailed (75.2%), the genotype Leu412Leu was less common — 2.9% (Ȥ 2 = 7.09; p = 0.03). In the group of healthy individuals, the distribution of genotypes was as follows: Phe412Phe — 60.4%, Phe412Leu — 30.2%, Leu412Leu — 9.4% (Ȥ 2 = 7.09; ɪ = 0.03). Carriers of allele -412Phe (OR = 2.08 [CI95%: 1.25–3.47]) and genotype Phe412Phe (OR = 2.08 [CI95%: 1.14–3.80]) are more likely to develop chickenpox. The probability of developing the disease for persons having the major allele A of the genotype TLR9 (Ⱥ2848G) is 0.29 [CI95%: 0.19– 0.43], for individuals with the mutant allele G of the genotype TLR9 (Ⱥ2848G) — 3.50 [CI95%: 2.32–5.29]. The prevalence of TLR9 (T1237C) in the main group was not signifi cantly different from that in the control group (p > 0.05). The probability of developing the disease for persons having the major allele A is 0.29 [95% CI 0.19–0.43], for carriers of the mutant allele G — 3.50 [95% CI 2.32-5.29]. When analyzing SNP TLR9 (A2848G), it was found that allele G prevailed with a frequency of 0.614, and allele A — with a frequency of 0.386, which is 1.9 times less than in the control group (Ȥ 2 = 36.67; p < 0.001). In patients group, homozygotes AA were found in 9.5% of cases, heterozygotes AG — in 58.1%, the rest cases were homozygous variants GG (Ȥ 2 = 40.11; p < 0.001). In the control group, all possible genotypes with a predominance of the heterozygous genotype AG were identifi ed and comprised 47.9%. When assessing the relative risk of gene variation associations connected with the development of chickenpox, we found that the polymorphism of genes TLR9 (A2848G) AG/GG increases the risk of the development of disease caused by varicella virus in the studied category by 3.4 times, and the polymorphism TLR3 (Phe412Leu) Phe/ Phe — by 1.42 times. The ROC analysis was carried out, the area under curve was 0.77 (95% CI0.70–0.83); p < 0.001; specifi city — 0.62; sensitivity — 0.8. The developed model, being a relatively good identifi er, has satisfactory properties as a discriminator.Conclusion. Our study suggests that allele -412Phe and homozygous variant Phe412Phe of gene TLR3 (Phe412Leu), as well as allele G and homozygous variant GG of gene TLR9 (A2848G) predispose to chickenpox development. Meanwhile, the allele -412Leu of gene TLR3 (Phe412Leu), allele A, and homozygous variant AA of gene TLR9 (A2848G) reduce the probability of chickenpox development.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
0.10
自引率
0.00%
发文量
37
审稿时长
8 weeks
期刊最新文献
Opportunities for improving personnel situation assessment in community pediatric services: a retrospective analytical descriptive study Postmortem tissue changes and dynamics of their impedance parameters: a preclinical experimental study Chronic endometritis and infertility — in vitro fertilization outcomes: systematic review and meta-analysis Clinical diagnostic approach in the treatment of chronic periodontitis in mandibular molars: Clinical cases Immune pathogenesis and immune therapy of a sclerosing variant of vulvar lichen sclerosus: a prospective cohort study
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1