Role of combinations of polymorphisms of cytokine genes in the diagnosis of Legg–Calve–Perthes disease in children
- Authors: Shabaldin N.A.1,2, Shabaldin A.V.1,3, Apalko S.V.4, Tsepokina A.V.3, Rovda Y.I.1
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Affiliations:
- Kemerovo State Medical University of the Ministry of Health of the Russian Federation
- Kuzbass Regional Children’s Clinical Hospital
- Institute for Complex Issues of Cardiovascular Diseases
- City Hospital No. 40 of the Kurortny District
- Issue: Vol 8, No 4 (2020)
- Pages: 395-406
- Section: Original Study Article
- URL: https://journals.eco-vector.com/turner/article/view/34927
- DOI: https://doi.org/10.17816/PTORS34927
- ID: 34927
Cite item
Abstract
Background. Legg–Calve–Perthes disease (LCPD) is an idiopathic avascular femoral head osteonecrosis. The early disease stage is associated with the development of synovitis of the hip joint linked to the overproduction of factors induced by hypoxia as well as of interleukin (IL)-6. Associations of individual polymorphic variants of cytokine genes with LCPD have been shown. Moreover, alterations in the cytokine regulatory cascade are considered an important link in the pathogenesis of synovial inflammation in the early stages of LCPD. Accordingly, this process may be associated with a certain combination of polymorphic variants of the genes for pro-inflammatory and anti-inflammatory cytokines.
Aim. This study aimed to study the associations of polymorphic variants of the genes for pro-inflammatory and anti-inflammatory IL with LCPD.
Materials and methods. In this case–control study, the main and control groups were composed of 26 children with LCPD and 40 healthy children (all aged 3–11 years), respectively. Genotyping of IL10 (rs1800896), IL13 (rs20541), IL18 (rs187238), IL18 (rs5744292), IL1a (rs1800587), IL1RA (POL_GF_58), IL-1Ra (rs4251961), IL1B (rs16944), IL1B (rs1143634), IL4 (POL_GF_59), IL4 (rs2243250), IL6 (rs1800796), IL6 (rs1800795), INFγ (rs2430561), TGFβ (rs1800469), and TNF (rs1800629) was performed by polymerase chain reaction (PCR) using TaqMan probes to the corresponding polymorphic variants of genes produced by Thermo Fisher Scientific (USA) on an amplifier ViiATM 7 RealTime PCR System (Life Technologies, USA). Statistical processing of the results was carried out using the SNPstats program and multifactor dimensionality reduction.
Results. The study revealed three separate LCPD-potentiating genotypes of polymorphic variants of cytokine genes: IL10 (rs1800896; T>C)*T/C (OR 6.50), IL4 (POL_GF_49, VNTR, Intron4)*2R/2R (OR 12.32), and IL-6 (rs1800796; G>C)*G/C (OR 4.08). Two polymorphic variants of the IL4 gene (POL_GF_49, VNTR, Intron4, and rs2243250; C>T) had a pronounced synergism with respect to the diagnosis of LCPD. Moderate synergy with respect to the diagnosis of LCPD demonstrated the intergenic interaction of IL6 (rs1800796, G>C) with tumor necrosis factor-α (rs1800629, G>A). Moderate antagonism between LCPD and intergenic interactions was obtained for polymorphic variants of IL18 (rs5744292, T>C) and transforming growth factor-β (rs1800469, A>G) genes.
Conclusions. The pathogenesis of synovitis and subsequent osteonecrosis in LCPD is associated with a combination of polymorphic variants of the genes of pro-inflammatory and anti-inflammatory cytokines, as well as of DNA variants of the pro-allergic IL4 gene.
Full Text
About the authors
Nikita A. Shabaldin
Kemerovo State Medical University of the Ministry of Health of the Russian Federation; Kuzbass Regional Children’s Clinical Hospital
Author for correspondence.
Email: Shabaldin.nk@yandex.ru
ORCID iD: 0000-0001-8628-5649
MD, PhD, Associate Professor of the Department of Child Surgical Diseases
Russian Federation, KemerovoAndrey V. Shabaldin
Kemerovo State Medical University of the Ministry of Health of the Russian Federation; Institute for Complex Issues of Cardiovascular Diseases
Email: weit2007@yandex.ru
ORCID iD: 0000-0002-8785-7896
MD, PhD, D.Sc., Associate Professor, Professor of the Department of Microbiology, Immunology and Virology
Russian Federation, KemerovoSvetlana V. Apalko
City Hospital No. 40 of the Kurortny District
Email: svetlana.apalko@gmail.com
ORCID iD: 0000-0002-3853-4185
PhD in biology, Head of the Biobanking and Translational Medicine Sector
Russian Federation, Saint PetersburgAnna V. Tsepokina
Institute for Complex Issues of Cardiovascular Diseases
Email: cepoav1991@gmail.com
ORCID iD: 0000-0002-4467-8732
MD, Junior Researcher of the Laboratory of Genomic Medicine
Russian Federation, KemerovoYuri I. Rovda
Kemerovo State Medical University of the Ministry of Health of the Russian Federation
Email: y.i.rovda@rambler.ru
ORCID iD: 0000-0001-8310-5868
MD, PhD, D.Sc., Professor, Professor of the Department of Pediatrics and Neonatology
Russian Federation, KemerovoReferences
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