CYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA

Atopic bronchial asthma (ABA) is a multifactorial disease; its development is dependent on many environmental and genetic factors. Genetic risk factors can affect the clinical phenotype of ABA and the level of therapeutic control over the disease. Cytokine genes are crucially important in pathogenes...

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Autores principales:	M. V. Smolnikova, M. B. Freidin, S. V. Smirnova
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2017
Materias:	atopy inflammation bronchial asthma cytokines gene polymorphism disease control Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/2dd2572b678041ce8a4b48cd3abe4c44
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spelling	oai:doaj.org-article:2dd2572b678041ce8a4b48cd3abe4c442021-11-18T08:03:46ZCYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA1563-06252313-741X10.15789/1563-0625-2017-5-605-614https://doaj.org/article/2dd2572b678041ce8a4b48cd3abe4c442017-10-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1362https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XAtopic bronchial asthma (ABA) is a multifactorial disease; its development is dependent on many environmental and genetic factors. Genetic risk factors can affect the clinical phenotype of ABA and the level of therapeutic control over the disease. Cytokine genes are crucially important in pathogenesis of ABA as they encode proteins participating in immune response and development of inflammation in bronchi. It was suggested that the therapeutic control of the disease is genetically mediated and depends on the presence of one or another allele in genes of mediators, participating in ABA pathogenesis. The knowledge about genetic markers will allow to predict clinical course of ABA in children. We carried out the analysis of association between genes of pro- and anti-inflammatory cytokines with the level of therapeutic control of ABA. In children with controlled and uncontrolled ABA (CABA and UABA, respectively; n = 110), and in general a population sample (n = 138), we analysed 11 polymorphisms: IL2 (rs2069762), IL4 (rs2070874 и rs2243250), IL5 (rs2069812), IL10 (rs1800872 and rs1800896), IL12B (rs3212227), TNFA (rs1800629 and rs1800630), TGFB1 (rs1800469), and IFNG (rs2069705), encoding cytokines actively participating at the development of allergic inflammation. According to results of present study, the prevalence of alleles and genotypes of the analysed loci in the East Siberia Caucasians is consistent with the data in other world Caucasian populations. We have found statistically significant differences between UABA and control groups for the prevalence of IL2 (rs2069762) polymorphism: GG genotype was more common in control group (14.1% compared to 5.9%, р = 0.03). It was shown that the IL2*T allele and ТТ genotype of the rs2069762 are associated with the increased risk of uncontrolled ABA. A comparison of the haplotypes of IL4 (rs2070874 and rs2243250) gene with correction for sex and age within an additive model revealed that the most common haplotype СC (prevalence in ABA/CABA/UABA groups is 0.75/0.76/0.74, respectively) is protective against the development of ABA (RR 0.53±0.32; p = 0.044). A comparative analysis of TNFA (rs1800629 and rs1800630) haplotypes has shown the GC haplotype to be protective against the risk of ABA (RR 0.59±0.17; р = 0.003) while the GA haplotype is positively associated with the disease (RR 2.07±0.25; р = 0.003). This was true for BA, regardless of the control over the disease (CABA GA: RR 1.93±1.2; p = 0.041; UABA GA: RR 2.43±0.31; p = 0.005). Thus, it was established that the studied cytokine genes are important for the development of ABA in children. These data were obtained for the first time for Caucasians of East Siberia. They are of interest in terms of accumulation of the data about the impact of cytokine genes polymorphism upon development of ABA and its therapeutic control in children.M. V. SmolnikovaM. B. FreidinS. V. SmirnovaSPb RAACIarticleatopyinflammationbronchial asthmacytokinesgene polymorphismdisease controlImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 19, Iss 5, Pp 605-614 (2017)
institution	DOAJ
collection	DOAJ
language	RU
topic	atopy inflammation bronchial asthma cytokines gene polymorphism disease control Immunologic diseases. Allergy RC581-607
spellingShingle	atopy inflammation bronchial asthma cytokines gene polymorphism disease control Immunologic diseases. Allergy RC581-607 M. V. Smolnikova M. B. Freidin S. V. Smirnova CYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA
description	Atopic bronchial asthma (ABA) is a multifactorial disease; its development is dependent on many environmental and genetic factors. Genetic risk factors can affect the clinical phenotype of ABA and the level of therapeutic control over the disease. Cytokine genes are crucially important in pathogenesis of ABA as they encode proteins participating in immune response and development of inflammation in bronchi. It was suggested that the therapeutic control of the disease is genetically mediated and depends on the presence of one or another allele in genes of mediators, participating in ABA pathogenesis. The knowledge about genetic markers will allow to predict clinical course of ABA in children. We carried out the analysis of association between genes of pro- and anti-inflammatory cytokines with the level of therapeutic control of ABA. In children with controlled and uncontrolled ABA (CABA and UABA, respectively; n = 110), and in general a population sample (n = 138), we analysed 11 polymorphisms: IL2 (rs2069762), IL4 (rs2070874 и rs2243250), IL5 (rs2069812), IL10 (rs1800872 and rs1800896), IL12B (rs3212227), TNFA (rs1800629 and rs1800630), TGFB1 (rs1800469), and IFNG (rs2069705), encoding cytokines actively participating at the development of allergic inflammation. According to results of present study, the prevalence of alleles and genotypes of the analysed loci in the East Siberia Caucasians is consistent with the data in other world Caucasian populations. We have found statistically significant differences between UABA and control groups for the prevalence of IL2 (rs2069762) polymorphism: GG genotype was more common in control group (14.1% compared to 5.9%, р = 0.03). It was shown that the IL2*T allele and ТТ genotype of the rs2069762 are associated with the increased risk of uncontrolled ABA. A comparison of the haplotypes of IL4 (rs2070874 and rs2243250) gene with correction for sex and age within an additive model revealed that the most common haplotype СC (prevalence in ABA/CABA/UABA groups is 0.75/0.76/0.74, respectively) is protective against the development of ABA (RR 0.53±0.32; p = 0.044). A comparative analysis of TNFA (rs1800629 and rs1800630) haplotypes has shown the GC haplotype to be protective against the risk of ABA (RR 0.59±0.17; р = 0.003) while the GA haplotype is positively associated with the disease (RR 2.07±0.25; р = 0.003). This was true for BA, regardless of the control over the disease (CABA GA: RR 1.93±1.2; p = 0.041; UABA GA: RR 2.43±0.31; p = 0.005). Thus, it was established that the studied cytokine genes are important for the development of ABA in children. These data were obtained for the first time for Caucasians of East Siberia. They are of interest in terms of accumulation of the data about the impact of cytokine genes polymorphism upon development of ABA and its therapeutic control in children.
format	article
author	M. V. Smolnikova M. B. Freidin S. V. Smirnova
author_facet	M. V. Smolnikova M. B. Freidin S. V. Smirnova
author_sort	M. V. Smolnikova
title	CYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA
title_short	CYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA
title_full	CYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA
title_fullStr	CYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA
title_full_unstemmed	CYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA
title_sort	cytokine genes as genetic markers of controlled and uncontrolled atopic bronchial asthma
publisher	SPb RAACI
publishDate	2017
url	https://doaj.org/article/2dd2572b678041ce8a4b48cd3abe4c44
work_keys_str_mv	AT mvsmolnikova cytokinegenesasgeneticmarkersofcontrolledanduncontrolledatopicbronchialasthma AT mbfreidin cytokinegenesasgeneticmarkersofcontrolledanduncontrolledatopicbronchialasthma AT svsmirnova cytokinegenesasgeneticmarkersofcontrolledanduncontrolledatopicbronchialasthma
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CYTOKINE GENES AS GENETIC MARKERS OF CONTROLLED AND UNCONTROLLED ATOPIC BRONCHIAL ASTHMA

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