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BMC Medical Genetics

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Open Access 01-12-2018 | Research article

Association of IL10 and TGFB single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population: a case control study

Authors: Sara Hanaei, Sina Abdollahzade, Maryam Sadr, Mohammad Hossein Mirbolouk, Alireza Khoshnevisan, Nima Rezaei

Published in: BMC Medical Genetics | Issue 1/2018

Abstract

Background

Considered as one of the major causes of low back pain, Intervertebral disc degeneration (IVDD) is caused by several genetic and environmental factors. As inflammation plays an important role in disc degeneration, the genetic changes in both inflammatory and anti-inflammatory genes may play causative roles in IVDD as well. Therefore, the interactions between inflammatory and anti-inflammatory cytokines and also other components of disc matrix would determine the degree of tissue destruction in disc degeneration. However, there is still controversy regarding the exact role of inflammation and disc homeostasis imbalance in pathophysiology of IVDD. Therefore, current study was conducted to investigate the role of IL-10 and TGF-β single nucleotide polymorphisms (SNP) in Iranian IVDD patients.

Methods

Seventy-six IVDD patients and 140 healthy controls were enrolled in this study. Genomic DNA from peripheral leukocytes was tested for 3 SNPs in IL10 (L-10 -1082G/A (rs1800896), IL-10 -819C/T (rs1800871), IL-10 -592A/C (rs1800872)) and 2 SNPs in TGF-β (TGF-β Codon 10 C/T (rs1982037), and TGF-β Codon 25 C/T (rs1800471) genes through PCR-SSP method. The extracted genomic DNA was genotyped for the aforementioned SNPs of interest using specific primers, which were coated in the cytokines KITs and based on the PCR-SSP method for sequencing.

Results

The ‘T’ allele of IL-10 -819C/T and the ‘C’ allele of IL-10 -592A/C were more prevalent among patients, whereas the ‘C’ and ‘A’ alleles of respective SNPs were significantly more frequent in controls. The genotypes including ‘CT’ of IL-10 -819C/T, ‘CA’ of IL-10 -592A/C, and ‘GA’ of IL-10 -1082A/G were more common among patients, while the ‘CC’ genotype of both IL-10 -819C/T and IL-10 -592A/C SNPs were more frequent in controls. In addition, the IL-10 haplotypes including ‘ACC’, ‘ATA’, and ‘ACA’ were significantly associated with disease. Meanwhile, the ‘TC’ haplotype of TGF-β was more common among patients as well.

Conclusions

The IL-10 SNPs were significantly associated with IVDD in Iranian population; which proposes that genomic alterations of anti-inflammatory cytokines could lead to homeostasis imbalance in intervertebral discs and degenerative changes.

Urban JP, Roberts S. Degeneration of the intervertebral disc. Arthritis Res Therapy. 2003;5(3):120–30. https://doi.org/10.1186/ar629.CrossRef

Kelempisioti A, Eskola PJ, Okuloff A, Karjalainen U, Takatalo J, Daavittila I, Niinimaki J, Sequeiros RB, Tervonen O, Solovieva S, et al. Genetic susceptibility of intervertebral disc degeneration among young Finnish adults. BMC Med Genet. 2011;12:153. https://doi.org/10.1186/1471-2350-12-153.CrossRefPubMedPubMedCentral

Urano T, Narusawa K, Shiraki M, Sasaki N, Hosoi T, Ouchi Y, Nakamura T, Inoue S. Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women. Eur Spine J. 2011;20(4):572–7. https://doi.org/10.1007/s00586-010-1598-0.CrossRefPubMed

Hanaei S, Abdollahzade S, Khoshnevisan A, Kepler CK, Rezaei N. Genetic aspects of intervertebral disc degeneration. Rev Neurosci. 2015;26(5):581–606. https://doi.org/10.1515/revneuro-2014-0077.CrossRefPubMed

Lin WP, Lin JH, Chen XW, Wu CY, Zhang LQ, Huang ZD, Lai JM. Interleukin-10 promoter polymorphisms associated with susceptibility to lumbar disc degeneration in a Chinese cohort. Genet Mol Res. 2011;10(3):1719–27. https://doi.org/10.4238/vol10-3gmr1283.CrossRefPubMed

Akyol S, Eraslan BS, Etyemez H, Tanriverdi T, Hanci M. Catabolic cytokine expressions in patients with degenerative disc disease. Turkish Neurosurg. 2010;20(4):492–9. https://doi.org/10.5137/1019-5149.JTN.3394-10.1.

Holm S, Mackiewicz Z, Holm AK, Konttinen YT, Kouri VP, Indahl A, Salo J. Pro-inflammatory, pleiotropic, and anti-inflammatory TNF-alpha, IL-6, and IL-10 in experimental porcine intervertebral disk degeneration. Vet Pathol. 2009;46(6):1292–300. https://doi.org/10.1354/vp.07-VP-0179-K-FL.CrossRefPubMed

Nerlich AG, Bachmeier BE, Boos N. Expression of fibronectin and TGF-beta1 mRNA and protein suggest altered regulation of extracellular matrix in degenerated disc tissue. Eur Spine J. 2005;14(1):17–26. https://doi.org/10.1007/s00586-004-0745-x.CrossRefPubMed

Freemont AJ. The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology (Oxford). 2009;48(1):5–10. https://doi.org/10.1093/rheumatology/ken396.CrossRef

10.

Murakami H, Yoon ST, Attallah-Wasif ES, Tsai KJ, Fei Q, Hutton WC. The expression of anabolic cytokines in intervertebral discs in age-related degeneration. Spine. 2006;31(16):1770–4. https://doi.org/10.1097/01.brs.0000227255.39896.f3.CrossRefPubMed

11.

Lee S, Moon CS, Sul D, Lee J, Bae M, Hong Y, Lee M, Choi S, Derby R, Kim BJ, et al. Comparison of growth factor and cytokine expression in patients with degenerated disc disease and herniated nucleus pulposus. Clin Biochem. 2009;42(15):1504–11. https://doi.org/10.1016/j.clinbiochem.2009.06.017.CrossRefPubMed

12.

Tomaszewski KA, Adamek D, Pasternak A, Glowacki R, Tomaszewska R, Walocha JA. Degeneration and calcification of the cervical endplate is connected with decreased expression of ANK, ENPP-1, OPN and TGF-beta1 in the intervertebral disc. Pol J Pathol. 2014;65(3):210–7. https://doi.org/10.5114/pjp.2014.45783.CrossRefPubMed

13.

Gruber HE, Hoelscher GL, Ingram JA, Bethea S, Zinchenko N, Hanley EN Jr. Variations in aggrecan localization and gene expression patterns characterize increasing stages of human intervertebral disk degeneration. Exp Mol Pathol. 2011;91(2):534–9. https://doi.org/10.1016/j.yexmp.2011.06.001.CrossRefPubMed

14.

Movahedi M, Mahdaviani SA, Rezaei N, Moradi B, Dorkhosh S, Amirzargar AA. IL-10, TGF-beta, IL-2, IL-12, and IFN-gamma cytokine gene polymorphisms in asthma. J Asthma. 2008;45(9):790–4. https://doi.org/10.1080/02770900802207261.CrossRefPubMed

15.

Najafi S, Firooze Moqadam I, Mohammadzadeh M, Bidoki AZ, Yousefi H, Farhadi E, Tonekaboni A, Meighani G, Amirzargar AA, Rezaei N. Interleukin-10 gene polymorphisms in recurrent aphthous stomatitis. Immunol Investig. 2014;43(4):405–9. https://doi.org/10.3109/08820139.2014.880119.CrossRef

16.

Nasiri R, Hirbod-Mobarakeh A, Movahedi M, Farhadi E, Ansaripour B, Amirzargar AA, Rezaei N. Gene polymorphisms of interleukin-10 and transforming growth factor beta in allergic rhinitis. Allergol Immunopathol. 2016;44(2):125–30. https://doi.org/10.1016/j.aller.2015.05.010.CrossRef

17.

Rezaei A, Ziaee V, Sharabian FT, Harsini S, Mahmoudi M, Soltani S, Sadr M, Moradinejad MH, Aghighi Y, Rezaei N. Lack of association between interleukin-10, transforming growth factor-beta gene polymorphisms and juvenile-onset systemic lupus erythematosus. Clin Rheumatol. 2015;34(6):1059–64. https://doi.org/10.1007/s10067-015-2877-2.CrossRefPubMed

18.

Rezaei N, Aghamohammadi A, Mahmoudi M, Shakiba Y, Kardar GA, Mahmoudi M, Moradi B, Amirzargar AA. Association of IL-4 and IL-10 gene promoter polymorphisms with common variable immunodeficiency. Immunobiology. 2010;215(1):81–7. https://doi.org/10.1016/j.imbio.2009.01.011.CrossRefPubMed

19.

Shahrokhi A, Zare-Shahabadi A, Soltani S, Soleimani F, Vameghi R, Konjkav AR, Karimi P, Katibeh P, Vafaei M, Zoghi S, et al. Association of TGFB, but not IL10, single nucleotide polymorphisms with febrile seizures. Seizure. 2015;29:148–52. https://doi.org/10.1016/j.seizure.2015.05.001.CrossRefPubMed

20.

Tavakol M, Movahedi M, Amirzargar AA, Aryan Z, Bidoki AZ, Heidari K, Soltani S, Gharagozlou M, Aghamohammadi A, Nabavi M, et al. Association of interleukin 10 and transforming growth factor beta gene polymorphisms with chronic idiopathic urticaria. Acta Dermatovenerol Croatica. 2014;22(4):239–45.

21.

Amirzargar AA, Naroueynejad M, Khosravi F, Dianat SS, Rezaei N, Mytilineos J, Nikbin B. Cytokine single nucleotide polymorphisms in Iranian populations. Eur Cytokine Netw. 2008;19(2):104–12. https://doi.org/10.1684/ecn.2008.0122.PubMed

22.

Loparev VN, Cartas MA, Monken CE, Velpandi A, Srinivasan A. An efficient and simple method of DNA extraction from whole blood and cell lines to identify infectious agents. J Virol Methods. 1991;34(1):105–12. https://doi.org/10.1016/0166-0934(91)90126-K.CrossRefPubMed

23.

Rodriguez S, Gaunt TR, Day IN. Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. 2009;169(4):505–14. https://doi.org/10.1093/aje/kwn359.CrossRefPubMedPubMedCentral

24.

Eskola P: The search for susceptibility genes in lumbar disc degeneration. faculty of medicine, institute of biomedicine; 2012.

25.

Lalani I, Bhol K, Ahmed AR. Interleukin-10: biology, role in inflammation and autoimmunity. Ann Allergy Asthma Immunol. 1997;79(6):469–83. https://doi.org/10.1016/S1081-1206(10)63052-9.CrossRefPubMed

26.

Noponen-Hietala N, Virtanen I, Karttunen R, Schwenke S, Jakkula E, Li H, Merikivi R, Barral S, Ott J, Karppinen J, et al. Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica. Pain. 2005;114(1–2):186–94. https://doi.org/10.1016/j.pain.2004.12.015.CrossRefPubMed

27.

Sowa G, Vadala G, Studer R, Kompel J, Iucu C, Georgescu H, Gilbertson L, Kang J. Characterization of intervertebral disc aging: longitudinal analysis of a rabbit model by magnetic resonance imaging, histology, and gene expression. Spine. 2008;33(17):1821–8. https://doi.org/10.1097/BRS.0b013e31817e2ce3.CrossRefPubMed

28.

Schroeder M, Viezens L, Schaefer C, Friedrichs B, Algenstaedt P, Ruther W, Wiesner L, Hansen-Algenstaedt N. Chemokine profile of disc degeneration with acute or chronic pain. J Neurosurg Spine. 2013;18(5):496–503. https://doi.org/10.3171/2013.1.SPINE12483.CrossRefPubMed

29.

Peng B, Chen J, Kuang Z, Li D, Pang X, Zhang X. Expression and role of connective tissue growth factor in painful disc fibrosis and degeneration. Spine. 2009;34(5):E178–82. https://doi.org/10.1097/BRS.0b013e3181908ab3.CrossRefPubMed

30.

Sakai Y, Matsuyama Y, Hasegawa Y, Yoshihara H, Nakamura H, Katayama Y, Imagama S, Ito Z, Ishiguro N, Hamajima N. Association of gene polymorphisms with intervertebral disc degeneration and vertebral osteophyte formation. Spine. 2007;32(12):1279–86. https://doi.org/10.1097/BRS.0b013e318059af8a.CrossRefPubMed

Title: Association of IL10 and TGFB single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population: a case control study
Authors: Sara Hanaei
Sina Abdollahzade
Maryam Sadr
Mohammad Hossein Mirbolouk
Alireza Khoshnevisan
Nima Rezaei
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-018-0572-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Association of IL10 and TGFB single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population: a case control study

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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