细胞因子基因多态性变异组合在测定儿童Legg-Calvet-Perthes病中的作用
- 作者: Shabaldin N.A.1,2, Shabaldin A.V.1,3, Apalko S.V.4, Tsepokina A.V.3, Rovda Y.I.1
-
隶属关系:
- 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
- 期: 卷 8, 编号 4 (2020)
- 页面: 395-406
- 栏目: Original Study Article
- ##submission.dateSubmitted##: 03.07.2020
- ##submission.dateAccepted##: 15.10.2020
- ##submission.datePublished##: 09.01.2021
- URL: https://journals.eco-vector.com/turner/article/view/34927
- DOI: https://doi.org/10.17816/PTORS34927
- ID: 34927
如何引用文章
详细
论证:Legg-Calvet-Perthes病以股骨头特发性坏死为特征。该疾病的早期阶段与缺氧引起的因子和白细胞介素6产生过多的髋关节滑膜炎的发展有关。细胞因子基因的个体多态性变异与Legg-Calvet-Perthes病的相关性也得到了证实。细胞因子调节串级紊乱是Legg-Calvet-Perthes病早期滑膜炎症发病机制的重要环节。因此,这一过程的确定将与促炎细胞因子和抗炎细胞因子基因多态性的某种组合有关。
目的是研究促炎和抗炎白细胞介素基因多态性与Legg-Calvet-Perthes病的关系。
材料与方法。该研究以病例对照形式进行。主要组为26例Legg-Calvet-Perthes病儿童,对照组为40例健康儿童(主要组和对照组年龄分别为3至11岁)。基因分型IL10 (rs1800896)、IL13 (rs20541)、IL18 (rs187238)、IL18 (rs5744292)、IL1a (rs1800587)、IL1RA (POL_GF_58)、IL1Ra (rs4251961)、IL1B (rs16944)、IL1B (rs1143634)、IL4 (POL_GF_59)、IL4 (rs2243250)、IL6 (rs1800796)、IL6 (rs1800795)、INFγ (rs2430561)、TGFβ (rs1800469)、TNF (rs1800629),通过使用TaqMan探针的聚合酶反应方法,对Thermo Thermo Scientific(美国)在ViiATM 7 RealTime PCR System的放大器(Life Technologies,美国)上生产的相应基因多态性变体进行分析。使用SNPstats程序和Multifactor Dimensionality Reduction对结果进行统计处理。
结果。细胞因子基因多态变异体的3种独立增强性Legg-Calvet-Perthes病基因型:IL10 (rs1800896;T>C)*T/C(优势率为6.50),IL4(POL_GF_49,VNTR,Intron4)*2R/2R(优势率为12.32),IL6(rs1800796;G>C)*G/C(优势率为4.08)。IL4的两个多态变异(POL_GF_49,VNTR,Intron4和rs2243250;C>T)与Legg-Calvet-Perthes病的测定有明显的协同作用。IL6(rs1800796;G>C)和TNFα(rs1800629,G>A)基因间相互作用证明了在Legg-Calvet-Perthes病的测定中存在中度协同作用。IL18(rs5744292,T>C)和TGFβ(rs1800469,A>G)多态变异基因在Legg-Calvet-Perthes病之间存在中度拮抗和基因间互作。
结果。因此,Legg-Calvet-Perthes的滑膜炎发病机制和随后的骨坏死与促炎细胞因子和抗炎细胞因子基因的多态变异体以及促过敏IL4基因的DNA变异体组合有关。
全文:
作者简介
Nikita Shabaldin
Kemerovo State Medical University of the Ministry of Health of the Russian Federation; Kuzbass Regional Children’s Clinical Hospital
编辑信件的主要联系方式.
Email: Shabaldin.nk@yandex.ru
ORCID iD: 0000-0001-8628-5649
MD, PhD, Associate Professor of the Department of Child Surgical Diseases
俄罗斯联邦, KemerovoAndrey 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
俄罗斯联邦, KemerovoSvetlana 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
俄罗斯联邦, Saint PetersburgAnna 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
俄罗斯联邦, KemerovoYuri 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
俄罗斯联邦, Kemerovo参考
- Srzentic S, Spasovski V, Spasovski D, et al. Association of gene variants in TLR4 and IL-6 genes with Perthes disease. Srpski arhiv za celokupno lekarstvo. 2014;142(7-8):450-456. https://doi.org/ 10.2298/sarh1408450s.
- Тепленький М.П., Чепелева М.В., Кузнецова Е.И. Болезнь Пертеса: иммунологические аспекты // Клиническая лабораторная диагностика. – 2020. – Т. 65. – № 4. – С. 239–243. [Teplen’kiy MP, Chepeleva MV, Kuznetsova EI. Perthes Disease: Immunological Aspects. Russian Clinical Laboratory Diagnostics. 2020;65(4):239-243. (In Russ.)]. https://doi.org/10.18821/0869-2084-2020-65-4-239-243.
- van Wijnen A, Adapala NS, Kim HKW. Comprehensive genome-wide transcriptomic analysis of immature articular cartilage following ischemic osteonecrosis of the femoral head in piglets. PLOS One. 2016;11(4):e0153174. https://doi.org/10.1371/journal.pone.0153174.
- Kim KM, Wagle S, Moon YJ, et al. Interferon β protects against avascular osteonecrosis through interleukin 6 inhibition and silent information regulator transcript-1 upregulation. Oncotarget. 2017;9(3):3562-3575. https://doi.org/10.18632/oncotarget.23337.
- Adapala NS, Yamaguchi R, Phipps M, et al. Necrotic bone stimulates proinflammatory responses in macrophages through the activation of Toll-like receptor 4. Am J Pathol. 2016;186(11):2987-2999. https://doi.org/10.1016/j.ajpath.2016.06.024.
- Azarpira MR, Ghilian MM, Sobhan MR, et al. Association of eNOS 27-bp VNTR, 894G>T and 786T>C polymorphisms with susceptibility to Legg-Calve-Perthes disease in Iranian children. J Orthop. 2019;16(2):137-140. https://doi.org/10.1016/j.jor.2019. 02.024.
- Azarpira MR, Ghilian MM, Sobhan MR, et al. Association of MTHFR and TNF-alpha genes polymorphisms with susceptibility to Legg-Calve-Perthes disease in Iranian children: A case-control study. J Orthop. 2018;15(4):984-987. https://doi.org/10.1016/j.jor.2018. 08.042.
- Yamaguchi R, Kamiya N, Adapala NS, et al. HIF-1-dependent IL-6 activation in articular chondrocytes initiating synovitis in femoral head ischemic osteonecrosis. J Bone Joint Surg Am. 2016;98(13):1122-1131. https://doi.org/10.2106/JBJS.15.01209.
- Kim HK. Pathophysiology and new strategies for the treatment of Legg-Calve-Perthes disease. J Bone Joint Surg Am. 2012;94(7):659-669. https://doi.org/10.2106/JBJS.J.01834.
- Kim HK, Morgan-Bagley S, Kostenuik P. RANKL inhibition: A novel strategy to decrease femoral head deformity after ischemic osteonecrosis. J Bone Miner Res. 2006;21(12):1946-1954. https://doi.org/10.1359/jbmr.060905.
- Kuroyanagi G, Adapala NS, Yamaguchi R, et al. Interleukin-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis in a murine model. Bone. 2018;116:221-231. https://doi.org/10.1016/j.bone.2018.08.011.
- Wang AH, Lam WJ, Han DY, et al. The effect of IL-10 genetic variation and interleukin 10 serum levels on Crohn’s disease susceptibility in a New Zealand population. Hum Immunol. 2011;72(5):431-435. https://doi.org/10.1016/j.humimm.2011.02.014.
- Fiorentino DF, Zlotnik A, Mosmann TR, et al. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991;147(11):3815-3822.
- Fernandes MT, Fernandes KB, Marquez AS, et al. Association of interleukin-6 gene polymorphism (rs1800796) with severity and functional status of osteoarthritis in elderly individuals. Cytokine. 2015;75(2):316-320. https://doi.org/10.1016/j.cyto.2015.07.020.
- Akbarian-Bafghi MJ, Dastgheib SA, Morovati-Sharifabad M, et al. Association of IL-6 -174G > C and -572G > C polymorphisms with risk of Legg-Calve-Perthes disease in Iranian children. Fetal Pediatr Pathol. 2019:1-8. https://doi.org/10.1080/15513815.2019.1693671.
- Amr K, El-Awady R, Raslan H. Assessment of the -174G/C (rs1800795) and -572G/C (rs1800796) interleukin 6 gene polymorphisms in Egyptian patients with rheumatoid arthritis. Open Access Maced J Med Sci. 2016;4(4):574-577. https://doi.org/10.3889/oamjms.2016.110.
- Li J, Lin LH, Wang J, et al. Interleukin-4 and interleukin-13 pathway genetics affect disease susceptibility, serum immunoglobulin E levels, and gene expression in asthma. Ann Allergy Asthma Immunol. 2014;113(2):173-179 e171. https://doi.org/10.1016/j.anai. 2014.05.004.
- Liu S, Li T, Liu J. Interleukin-4 rs2243250 polymorphism is associated with asthma among Caucasians and related to atopic asthma. Cytokine. 2012;59(2):364-369. https://doi.org/10.1016/j.cyto.2012.05.006.
- Al-Eitan LN, Rababa’h DM, Alghamdi MA, Khasawneh RH. The influence of an IL-4 variable number tandem repeat (VNTR) polymorphism on breast cancer susceptibility. Pharmgenomics Pers Med. 2019;12:201-207. https://doi.org/10.2147/PGPM.S220571.
- Dziedziejko V, Kurzawski M, Paczkowska E, et al. The impact of IL18 gene polymorphisms on mRNA levels and interleukin-18 release by peripheral blood mononuclear cells. Postepy Hig Med Dosw (Online). 2012;66: 409-414. https://doi.org/10.5604/17322693.1000980.
- Harsanyi S, Zamborsky R, Krajciova L, et al. Developmental dysplasia of the hip: A review of etiopathogenesis, risk factors, and genetic aspects. Medicina (Kaunas). 2020;56(4). https://doi.org/10.3390/medicina56040153.