Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive losses

Prevalence of threatened miscarriage is 16-25% of all pregnancies. The symptomatics of the threatened miscarriage in the first trimester may develop due to conversion of initial inflammatory reaction that disturbs the intersystemic and local interactions in the endometrium, followed by placental ins...

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Main Authors: E. A. Tatarkova, A. R. Tuguz, A. A. Tsikunib, D. S. Shumilov, I. V. Smolkov, K. A. Rudenko, D. V. Muzhenya
Format: Article
Language:Russian
Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 2020-01-01
Series:Медицинская иммунология
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Online Access:https://www.mimmun.ru/mimmun/article/view/1741
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author E. A. Tatarkova
A. R. Tuguz
A. A. Tsikunib
D. S. Shumilov
I. V. Smolkov
K. A. Rudenko
D. V. Muzhenya
author_facet E. A. Tatarkova
A. R. Tuguz
A. A. Tsikunib
D. S. Shumilov
I. V. Smolkov
K. A. Rudenko
D. V. Muzhenya
author_sort E. A. Tatarkova
collection DOAJ
description Prevalence of threatened miscarriage is 16-25% of all pregnancies. The symptomatics of the threatened miscarriage in the first trimester may develop due to conversion of initial inflammatory reaction that disturbs the intersystemic and local interactions in the endometrium, followed by placental insufficiency, intrauterine fetal affection and spontaneous abortion. The aim of our work was to study the association between single nucleotide polymorphisms (SNPs) of some cytokine genes, e.g., IL-1β (C511T, rs16944), IL-17A (G197A, rs2275913), IL-12B (A1188C, rs3212227), TNFα (G308A, rs1800629), and IL-4 (C589T, rs2243250) and the risk of early reproductive losses among residents of Adyghe Republic (RA). The work was carried out at the Immunogenetic Laboratory of our Research Institute of Complex Problems. The allelic variants of cytokine genes were detected by SNP-method in 106 samples of genomic DNA in women with the threatened abortion in 1st trimester (n = 58) and the uncomplicated gestation (n = 48). SNP-typing of polymorphic variants of cytokine genes IL-1β, IL-17A, IL-12B, TNFα and IL-4 was carried out by PCR (polymerase chain reaction) with allele-specific primers and electrophoretic detection of results on test systems of (Litech, Moscow). Statistical analysis of experimental data was carried out by SPSS Statistical program 17.0. The correspondence of SNP distributions to expected values at Hardy—Weinberg equilibrium and comparison of allelic variants/ genotypes frequencies were performed using the χ2 criterion (Chi-square with Yates correction), odd ratios (OR) detected at significance level p < 0.05 and 95% confidence interval (95% CI). Reliability of the differences for the SNP frequencies for small samples was evaluated using the Fisher’s exact criterion. Heterozygous variant (C511T; OR = 3.46; 95% Cl: 1.04-11.54) and homozygous “mutant” genotypes (T511T; OR = 5.71; 95% Cl: 1.12-29.09) of the main proinflammatory IL-1β was significantly associated (p < 0.05) with the risk of developing threatening miscarriage in the Adygea residents. The -511Т allele of IL-1β gene, and -1188C variant of IL-12B gene increase the risk of the early termination of pregnancy, respectively, 5.8-fold (95% Cl: 2.4213.92; p = 0.00004), and 2.97-fold (95% Cl: 1.23-7.19; p = 0.01). The “mutant” -511T allelic variant of the IL-1 p gene is associated with the risk of developing a symptome complex of threatening miscarriage in Russian ethnic group (p = 0.0001; OR = 14.09), and in Adygea ethnic group (p = 0.02; OR = 8.17), which is almost undetectable in women with normal pregnancy in the first trimester. Thus, only С511Т (rs16944) in IL-1β gene and A1188C (rs3212227) in IL-12B gene of the five typed cytokine genes may be used as marker polymorphisms of gestational distress for the women in Adygea.
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spelling doaj.art-9a8ef8f989da432b8bcea26af71011182024-04-22T13:07:45ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2020-01-012161179118610.15789/1563-0625-2019-6-1179-11861238Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive lossesE. A. Tatarkova0A. R. Tuguz1A. A. Tsikunib2D. S. Shumilov3I. V. Smolkov4K. A. Rudenko5D. V. Muzhenya6Republican Natural-Mathematical SchoolAdyghe State UniversityMaikop City Clinical HospitalRepublican Natural-Mathematical SchoolMaikop State Technological UniversityMaikop State Technological UniversityMaikop State Technological UniversityPrevalence of threatened miscarriage is 16-25% of all pregnancies. The symptomatics of the threatened miscarriage in the first trimester may develop due to conversion of initial inflammatory reaction that disturbs the intersystemic and local interactions in the endometrium, followed by placental insufficiency, intrauterine fetal affection and spontaneous abortion. The aim of our work was to study the association between single nucleotide polymorphisms (SNPs) of some cytokine genes, e.g., IL-1β (C511T, rs16944), IL-17A (G197A, rs2275913), IL-12B (A1188C, rs3212227), TNFα (G308A, rs1800629), and IL-4 (C589T, rs2243250) and the risk of early reproductive losses among residents of Adyghe Republic (RA). The work was carried out at the Immunogenetic Laboratory of our Research Institute of Complex Problems. The allelic variants of cytokine genes were detected by SNP-method in 106 samples of genomic DNA in women with the threatened abortion in 1st trimester (n = 58) and the uncomplicated gestation (n = 48). SNP-typing of polymorphic variants of cytokine genes IL-1β, IL-17A, IL-12B, TNFα and IL-4 was carried out by PCR (polymerase chain reaction) with allele-specific primers and electrophoretic detection of results on test systems of (Litech, Moscow). Statistical analysis of experimental data was carried out by SPSS Statistical program 17.0. The correspondence of SNP distributions to expected values at Hardy—Weinberg equilibrium and comparison of allelic variants/ genotypes frequencies were performed using the χ2 criterion (Chi-square with Yates correction), odd ratios (OR) detected at significance level p < 0.05 and 95% confidence interval (95% CI). Reliability of the differences for the SNP frequencies for small samples was evaluated using the Fisher’s exact criterion. Heterozygous variant (C511T; OR = 3.46; 95% Cl: 1.04-11.54) and homozygous “mutant” genotypes (T511T; OR = 5.71; 95% Cl: 1.12-29.09) of the main proinflammatory IL-1β was significantly associated (p < 0.05) with the risk of developing threatening miscarriage in the Adygea residents. The -511Т allele of IL-1β gene, and -1188C variant of IL-12B gene increase the risk of the early termination of pregnancy, respectively, 5.8-fold (95% Cl: 2.4213.92; p = 0.00004), and 2.97-fold (95% Cl: 1.23-7.19; p = 0.01). The “mutant” -511T allelic variant of the IL-1 p gene is associated with the risk of developing a symptome complex of threatening miscarriage in Russian ethnic group (p = 0.0001; OR = 14.09), and in Adygea ethnic group (p = 0.02; OR = 8.17), which is almost undetectable in women with normal pregnancy in the first trimester. Thus, only С511Т (rs16944) in IL-1β gene and A1188C (rs3212227) in IL-12B gene of the five typed cytokine genes may be used as marker polymorphisms of gestational distress for the women in Adygea.https://www.mimmun.ru/mimmun/article/view/1741threatened miscarriagesnps of cytokine genesil-17a (g197ars2275913)il-1β (с511тrs16944)il-4 (c589trs2243250)tnfα (g308ars1800629)il-12b (a1188crs3212227)
spellingShingle E. A. Tatarkova
A. R. Tuguz
A. A. Tsikunib
D. S. Shumilov
I. V. Smolkov
K. A. Rudenko
D. V. Muzhenya
Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive losses
Медицинская иммунология
threatened miscarriage
snps of cytokine genes
il-17a (g197a
rs2275913)
il-1β (с511т
rs16944)
il-4 (c589t
rs2243250)
tnfα (g308a
rs1800629)
il-12b (a1188c
rs3212227)
title Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive losses
title_full Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive losses
title_fullStr Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive losses
title_full_unstemmed Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive losses
title_short Gene polymorphisms of IL-1β (C511T), IL-17A (G197A), IL-12B (A1188C), TNFα (G308A) and IL-4 (C589T) associated with threat of early reproductive losses
title_sort gene polymorphisms of il 1β c511t il 17a g197a il 12b a1188c tnfα g308a and il 4 c589t associated with threat of early reproductive losses
topic threatened miscarriage
snps of cytokine genes
il-17a (g197a
rs2275913)
il-1β (с511т
rs16944)
il-4 (c589t
rs2243250)
tnfα (g308a
rs1800629)
il-12b (a1188c
rs3212227)
url https://www.mimmun.ru/mimmun/article/view/1741
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