Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Oral Health
Published in: BMC Oral Health 1/2016

Open Access 01-12-2016 | Research article

Association of genetic polymorphisms in interferon-γ, interleukin-6 and transforming growth factor-β1 gene with oral lichen planus susceptibility

Authors: Maha Ali M. Al-Mohaya, Lubna Al-Otaibi, Fahad Al-Harthi, Ebtissam Al Bakr, Misbahul Arfin, Abdulrahman Al-Asmari

Published in: BMC Oral Health | Issue 1/2016

Login to get access

Abstract

Background

Oral lichen planus (OLP) is a premalignant mucocutaneous disease in which genetic factors and immune responses play a major role. Cytokines play an important role in the pathogenesis and disease progression of OLP. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-β1 on OLP susceptibility in a Saudi cohort.

Methods

Forty two unrelated patients with OLP and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms.

Results

The frequency of genotype AT of IFN-γ (874A/T) was significantly higher while genotype AA was lower in OLP patients as compared to controls (P < 0.05). The frequency of T containing genotypes (AT + TT) was also higher in OLP patients as compared to that in controls (P = 0.003). The frequencies of allele T was higher while that of allele A lower in patients than the controls however the difference was not statistically significant (P = 0.07). There was no significant difference in the frequencies of alleles and genotypes of IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms between patient and control groups. These results indicated that genotype AT of IFN-γ (874A/T) polymorphism is associated with OLP risk and genotype AA is protective to OLP. On the other hand the polymorphisms IL-6 (174G/C) and TGF-β1 (509C/T) may not be associated with OLP risk in our population.

Conclusion

It is concluded that IFN-γ (874A/T) polymorphism is associated with the susceptibility of OLP, however further studies with large sample size involving different ethnic populations should be conducted to strengthen our results.
Literature
1.
Sugerman PB, Savage NW, Walsh LJ, Zhao ZZ, Zhou XJ, Khan A, et al. The pathogenesis of oral lichen planus. Crit Rev Oral Biol Med. 2002;13(4):350–65.CrossRefPubMed
2.
Khan A, Farah CS, Savage NW, Walsh LJ, Harbrow DJ, Sugerman PB. Th1 cytokines in oral lichen planus. J Oral Pathol Med. 2003;32(2):77–83.CrossRefPubMed
3.
Tao X, Li C, Rhodus NL, Xia J, Yang X, Cheng B. Simultaneous detection of IFN-gamma and IL-4 in lesional tissues and whole unstimulated saliva from patients with oral lichen planus. J Oral Pathol Med. 2008;37(2):83–7.CrossRefPubMed
4.
Carrozzo M. Understanding the pathobiology of oral lichen planus. Curr Oral Health Rep. 2014;1:173–9.CrossRef
5.
Farhi D, Dupin N. Pathophysiology, etiologic factors, and clinical management of oral lichen planus, part I: facts and controversies. Clin Dermatol. 2010;28(1):100–8.CrossRefPubMed
6.
Gonzalez-Moles MA, Scully C, Gil-Montoya JA. Oral lichen planus: controversies surrounding malignant transformation. Oral Dis. 2008;14(3):229–43.CrossRefPubMed
7.
Bermejo-Fenoll A, Sánchez-Siles M, López-Jornet P, Camacho-Alonso F, Salazar-Sánchez NJ. A retrospective clinicopathological study of 550 patients with oral lichen planus in south-eastern Spain. Oral Pathol Med. 2010;39(6):49–6.CrossRef
8.
Jin X, Wang J, Zhu L, Wang L, Dan X, Zeng X, et al. Association between −308 G/A polymorphism in TNF-α gene and lichen planus: a meta-analysis. J Dermatol Sci. 2012;68(3):127–34.CrossRefPubMed
9.
Al-Mohaya MA, Al-Harthi F, Arfin M, Al-Asmari A. TNF-α, TNF-β and IL-10 gene polymorphism and association with oral lichen planus risk in Saudi patients. J Appl Oral Sci. 2015;23(3):295–301.CrossRefPubMedPubMedCentral
10.
Lu R, Zhang J, Sun W, Du G, Zhou G. Inflammation-related cytokines in oral lichen planus: an overview. J Oral Pathol Med. 2015;44(1):1–14.CrossRefPubMed
11.
Calvo J, Martínez N, Etxagibel A, Calleja S, Sáez-torres C, Sedeño M, Julià R, Muncunill J, Matamoros N, Gayà A. Allelic frequencies of polymorphic variants of cytokine genes (IL1A, IL1B, IL1RN, IL6, IL10, IL12p40, and IFNG) in a Spanish population. Inmunologia. 2002;21(2):76–86.
12.
Pravica V, Perrey C, Stevens A, Lee J-H, Hutchinson IV. A single nucleotide polymorphism in the first intron of the human IFN-g gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-g production. Hum Immunol. 2000;61(9):863–66.CrossRefPubMed
13.
Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344(12):907–16.CrossRefPubMed
14.
Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102(7):1369–76.CrossRefPubMedPubMedCentral
15.
Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000;275(24):18138–44.CrossRefPubMed
16.
Hsu HJ, Yang YH, Shieh TY, Chen CH, Kao YH, Yang CF, Ko EC. Role of cytokine gene (interferon-γ, transforming growth factor-β1, tumor necrosis factor-α, interleukin-6, and interleukin-10) polymorphisms in the risk of oralprecancerous lesions in Taiwanese. Kaohsiung J Med Sci. 2014;30(11):551–8.CrossRefPubMed
17.
Xavier GM, de Sá AR, Guimarães AL, da Silva TA, Gomez RS. Investigation of functional gene polymorphisms interleukin-1beta, interleukin-6, interleukin-10 and tumor necrosis factor in individuals with oral lichen planus. J Oral Pathol Med. 2007;36(8):476–81.CrossRefPubMed
18.
Smith GH. TGF-beta and functional differentiation. J Mammary Gland Biol Neoplasia. 1996;1(4):343–52.CrossRefPubMed
19.
Clark DA, Coker R. Transforming growth factor beta (TGT-beta). Int J Biochem Cell Biol. 1998;30(3):293–98.CrossRefPubMed
20.
Shah R, Hurley CK, Posch PE. A molecular mechanism for the differential regulation of TGF-beta1 expression due to the common SNP − 509C-T (c-1347C > T). Hum Genet. 2006;120(4):461–9.CrossRefPubMed
21.
Meng J, Thongngarm T, Nakajima M, Yamashita N, Ohta K, Bates CA. Association of transforming growth factorbeta1 single nucleotide polymorphism C-509T with allergy and immunological activities. Arch Allergy Immunol. 2005;138(2):151–60.CrossRef
22.
Pulleyn LJ, Newton R, Adcock IM, Barnes PJ. TGFbeta1 allele association with asthma severity. Hum Genet. 2001;109(6):623–7.CrossRefPubMed
23.
Karadeniz M, Erdogan M, Berdeli A, Yilmaz C. Association of interleukin-6 − 174 G > C promoter polymorphism with increased risk of type 2 diabetes mellitus patients with diabetic nephropathy in Turkey. Genet Test Mol Bioma. 2014;18(1):62–5.CrossRef
24.
Schallreuter KU, Levenig C, Kühnl P, Löliger C, Hohl-Tehari M, Berger J. Histocompatibility antigens in vitiligo: Hamburg study on 102 patients from northern Germany. Dermatology. 1993;187(3):186–92.CrossRefPubMed
25.
26.
Carrozzo M, Uboldi de Capei M, Dametto E, Fasano ME, Arduino P, Broccoletti R, et al. Tumor necrosis factor-alpha and interferon-gamma polymorphisms contribute to susceptibility to oral lichen planus. J Invest Dermatol. 2004;122(1):87–94.CrossRefPubMed
27.
Bai J, Lin M, Zeng X, Zhang Y, Wang Z, Shen J, Jiang L, Gao F, Chen Q. Association of polymorphisms in the human IFN-gamma and IL-4 gene with oral lichen planus: a study in an ethnic Chinese cohort. J Interferon Cytokine Res. 2008;28(6):351–8.CrossRefPubMed
28.
Kimkong I, Nakkuntod J, Sodsai P, Hirankarn N, Kitkumthorn N. Association of interferon-gamma gene polymorphisms with susceptibility to oral lichen planus in the Thai population. Arch Oral Biol. 2012;57(5):491–4.CrossRefPubMed
29.
Lee YH, Bae SC. Association between interferon-c þ874 T/A polymorphism and susceptibility to autoimmune diseases: a meta-analysis. Lupus. 2015;0:1–9.
30.
Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A. 1997;94(7):3195–9.CrossRefPubMedPubMedCentral
31.
Hoffmann SC, Stanley EM, Darrin Cox E, Craighead N, DiMercurio BS, Koziol DE, et al. Association of cytokine polymorphic inheritance, in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation. 2001;72(8):1444–50.CrossRefPubMed
32.
Fayyazi A, Schweyer S, Soruri A, Duong LQ, Radzun HJ, Peters J, Parwaresch R, Berger H. T lymphocytes and altered keratinocytes express interferon-gamma and interleukin 6 in lichen planus. Arch Dermatol Res. 1999;291(9):485–90.CrossRefPubMed
33.
Karagouni EE, Dotsika EN, Sklavounou A. Alteration in peripheral blood mononuclear cell function and serum cytokines in oral lichen planus. J Oral Pathol Med. 1994;23(1):28–35.CrossRefPubMed
34.
Halma MA, Wheelhouse NM, Barber MD, Powell JJ, Fearon KC, Ross JA. Interferon-gamma polymorphisms correlate with duration of survival in pancreatic cancer. Hum Immunol. 2004;65(11):1405–8.CrossRefPubMed
35.
Hu X, Ivashkiv LB. Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases. Immunity. 2009;31(4):539–50.CrossRefPubMedPubMedCentral
36.
Szabo SJ, Sullivan BM, Peng SL, Glimcher LH. Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol. 2003;21:713–58.CrossRefPubMed
37.
Piccinni MP, Lombardelli L, Logiodice F, Tesi D, Kullolli O, Biagiotti R, et al. Potential pathogenetic role of Th17, Th0, and Th2 cells in erosive and reticular oral lichen planus. Oral Dis. 2014;20(2):212–8.CrossRefPubMed
38.
Xie S, Ding L, Xiong Z, Zhu S. Implications of Th1 and Th17 cells in pathogenesis of oral lichen planus. J Huazhong Univ Sci Technolog Med Sci. 2012;32(3):451–7.CrossRefPubMed
39.
Youngnak-Piboonratanakit P, Dhanuthai K, Thongprasom K, et al. Expression of IFN-gamma before and after treatment of oral lichen planus with 0.1% fluocinolone acetonide in orabase. J Oral Pathol Med. 2009;38(9):689–94.CrossRefPubMed
40.
41.
Prime SS, Pring M, Davies M, Paterson IC. TGF-beta signal transduction in oro-facial health and non-malignant disease (part I). Crit Rev Oral Biol Med. 2004;15(6):324–36.CrossRefPubMed
42.
Zhang J, Zhou G. Green tea consumption: an alternative approach to managing oral lichen planus. Inflamm Res. 2012;61(6):535–9.CrossRefPubMed
43.
Noori-Daloii MR, Rashidi-Nezhad A, Izadi P, Hossein-Nezhad A, Sobhani M, Derakhshandeh-Peykar P, et al. Transforming growth factor-beta1 codon 10 polymorphism is associated with acute GVHD after allogenic BMT in Iranian population. Ann Transplant. 2007;12(4):5–10.PubMed
44.
Castillejo A, Mata-Balaguer T, Guarinos C, Castillejo MI, Martínez-Cantó A, Barberá VM, et al. The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case–control study. BMC Cancer. 2009;9:406. doi:10.​1186/​1471-2407-9-406.CrossRefPubMedPubMedCentral
45.
Qian B, Katsaros D, Lu L, Preti M, Durando A, Arisio R, et al. High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-beta1. Breast Cancer Res Treat. 2009;117(1):131–40.CrossRefPubMed
46.
Angelo HD, Gomes Silva IIF, Oliveira RD, Louzada-Júnior P, Donadi EA, Crovella S, et al. Interleukin-18, interleukin- 12B and interferon gamma gene polymorphisms in Brazilian patients with rheumatoid arthritis: a pilot study. Tissue Antigens. 2015;86:276–8.CrossRefPubMed
47.
Silva GA, Naveca FG, Ramasawmy R, Boechat AL. Association between the IFNG þ874A/T gene polymorphism and leprosy resistance: a meta-analysis. Cytokine. 2014;65(2):130–3.CrossRefPubMed
48.
Wastowski IJ, Sampaio-Barros PD, Martelli-Palomino G, Marques-Neto JF, Crispim JC, Rassi DM, et al. Association of interferon-gamma gene polymorphism (þ874 T/A) with systemic sclerosis. Dis Markers. 2009;27(2):93–5.CrossRefPubMedPubMedCentral
49.
Cantor MJ, Nickerson P, Bernstein CN. The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease. Am J Gastroenterol. 2005;100(5):1134–42.CrossRefPubMed
50.
51.
Xu H, Li W, Fu H, Jiang G. Interferon-gamma gene polymorphism +874 (a/t) in Chinese children with Henoch-Schonlein purpura. Iran J Allergy Asthma Immunol. 2014;13(3):184–9.PubMed
52.
Chen X, Xu J, Chen Z, Zhou Z, Feng X, Zhou Y, et al. Interferon-gamma þ874A/T and interleukin-4 intron3 VNTR gene polymorphisms in Chinese patients with idiopathic thrombocytopenic purpura. Eur J Haematol. 2007;79(3):191–7.CrossRefPubMed
53.
Mosaad YM, Soliman OE, Tawhid ZE, Sherif DM. Interferon-gamma +874 T⁄A and interleukin-10 - 1082 A⁄G single nucleotide polymorphism in Egyptian children with tuberculosis. Scand J Immunol. 2010;72(4):358–64.CrossRefPubMed
54.
Elsaid A, Helaly MA, Hatata EZ, Fouda O, Settin A. TNF-α-308 and INF-γ + 874 gene polymorphisms in relation to susceptibility and severity of type 2 diabetes mellitus among Egyptian cases. Eur J Gen Med. 2012;9(3):173–7.
55.
Pertovaara M, Antonen J, Hurme M. Th2 cytokine genotypes are associated with a milder form of primary Sjogren’s syndrome. Ann Rheum Dis. 2006;65(5):666–70.CrossRefPubMed
56.
Spriewald BM, Witzke O, Wassmuth R, Wenze RR, Arnold ML, Philipp T, et al. Distinct tumour necrosis factor alpha, interferon gamma, interleukin 10, and cytotoxic T cell antigen 4 gene polymorphisms in disease occurrence and end stage renal disease in Wegener’s granulomatosis. Ann Rheum Dis. 2005;64(3):457–61.CrossRefPubMedPubMedCentral
57.
Tsiavou A, Hatziagelaki E, Chaidaroglou A, Koniavitou K, Degiannis D, Raptis SA. Correlation between intracellular interferon- gamma (IFN-gamma) production by CD4þ and CD8þ lymphocytes and IFN-gamma gene polymorphism in patients with type 2 diabetes mellitus and latent autoimmune diabetes of adults (LADA). Cytokine. 2005;31(2):135–41.CrossRefPubMed
58.
Dwivedi M, Laddha NC, Shah K, Shah BJ, Begum R. Involvement of interferon-gamma genetic variants and intercellular adhesion molecule-1 in onset and progression of generalized vitiligo. J Interferon Cytokine Res. 2013;33(11):646–59.CrossRefPubMedPubMedCentral
59.
Mishra N, Arankalle VA. Association of polymorphisms in the promoter regions of TNF-α (−308) with susceptibility to hepatitis E virus and TNF-α (−1031) and 16 IFN-γ (+874) genes with clinical outcome of hepatitis E infection in India. J Hepatol. 2011;55(6):1227–34.CrossRefPubMed
60.
Rekha PL, Ishaq M, Valluri V. A differential association of interferon-gamma high-producing allele T and low-producing allele A (þ874 A/T) with Hashimoto’s thyroiditis and Graves’ disease. Scand J Immunol. 2006;64(4):438–43.CrossRefPubMed
61.
Shokrgozar MA, Sarial S, Amirzargar A, Shokri F, Rezaei N, Arjang Z, et al. IL-2, IFN-gamma, and IL-12 gene polymorphisms and susceptibility to multiple sclerosis. J Clin Immunol. 2009;29(6):747–51.CrossRefPubMed
62.
Namian AM, Shahbaz S, Salmanpoor R, Namazi MR, Dehghani F, Kamali-Sarvestani E. Association of interferon-gamma and tumor necrosis factor alpha polymorphisms with susceptibility to vitiligo in Iranian patients. Arch Dermatol Res. 2009;301(1):21–5.CrossRefPubMed
63.
Ben-Ari Z, Mor E, Papo O, Kfir B, Sulkes J, Tambur AR, et al. Cytokine gene polymorphisms in patients infected with hepatitis B virus. Am J Gastroenterol. 2003;98(1):144–50.CrossRefPubMed
64.
Falleti E, Fabris C, Toniutto P, Fontanini E, Cussigh A, Caldato M, et al. Genetic polymorphisms of inflammatory cytokines and liver fibrosis progression due to recurrent hepatitis C. J Interferon Cytokine Res. 2007;27(3):239–46.CrossRefPubMed
65.
Migita K, Miyazoe S, Maeda Y, Daikoku M, Abiru S, Ueki T, et al. Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection – association between TGF-beta1 polymorphisms and hepatocellular carcinoma. J Hepatol. 2005;42(4):505–10.CrossRefPubMed
66.
Cheong JY, Cho SW, Chung SG, Lee JA, Yeo M, Wang HJ, et al. Genetic polymorphism of interferon-gamma, interferon-gamma receptor, and interferon regulatory factor-1 genes in patients with hepatitis B virus infection. Biochem Genet. 2006;44(5–6):246–55.CrossRefPubMed
67.
Baran W, Szepietowski JC, Mazur G, Baran E. IFN-gamma promoter gene polymorphism in psoriasis vulgaris. Biomarkers. 2008;13(1):52–8.CrossRefPubMed
68.
Tangwattanachuleeporn M, Sodsai P, Avihingsanon Y, Wongpiyabovorn J, Wongchinsri J, Hirankarn N. Association of interferon-gamma gene polymorphism (+874A) with arthritis manifestation in SLE. Clin Rheumatol. 2007;26(11):1921–4.CrossRefPubMed
69.
Nakkuntod J, Wongsurawat T, Charoenwongse P, Snabboon T, Sridama V, Hirankarn N. Association of TNF-alpha, TNF-beta, IFN-gamma and IL-1Ra gene polymorphisms with Graves’ disease in the Thai population. Asian Pac J Allergy Immunol. 2006;24(4):207–11.PubMed
70.
Bouzgarrou N, Hassen E, Farhat K, Bahri O, Gabbouj S, Maamouri N, et al. Combined analysis of interferon-gamma and interleukin-10 gene polymorphisms and chronic hepatitis C severity. Hum Immunol. 2009;70(4):230–6.CrossRefPubMed
71.
Col-Araz N, Pehlivan S, Baspinar O, Oguzkan-Balci S, Sever T, Balat A. Role of cytokine gene (IFN-gamma, TNF-alpha, TGFbeta1, IL-6, and IL-10) polymorphisms in pathogenesis of acute rheumatic fever in Turkish children. Eur J Pediatr. 2012;171(7):1103–8.CrossRefPubMed
72.
Pehlivan M, Okan V, Sever T, Balci SO, Yilmaz M, Babacan T, et al. Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura. Platelets. 2011;22(8):588–95.CrossRefPubMed
73.
Korachi M, Ceran N, Adaleti R, Nigdelioglu A, Sokmen M. An association study of functional polymorphic genes IRF-1, IFNGR-1, and IFN-gamma with disease progression, aspartate aminotransferase, alanine aminotransferase, and viral load in chronic hepatitis B and C. Int J Infect Dis. 2013;17(1):e44–9.CrossRefPubMed
Metadata
Title
Association of genetic polymorphisms in interferon-γ, interleukin-6 and transforming growth factor-β1 gene with oral lichen planus susceptibility
Authors
Maha Ali M. Al-Mohaya
Lubna Al-Otaibi
Fahad Al-Harthi
Ebtissam Al Bakr
Misbahul Arfin
Abdulrahman Al-Asmari
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2016
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-016-0277-x

Other articles of this Issue 1/2016

BMC Oral Health 1/2016 Go to the issue

Research article

HSP70 mRNA expression by cells of the epithelial rest of Malassez due to mechanical forces in vitro

Research article

Water fluoridation and ethnic inequities in dental caries profiles of New Zealand children aged 5 and 12–13 years: analysis of national cross-sectional registry databases for the decade 2004–2013

Research article

Oral behavior, dental, periodontal and microbiological findings in patients undergoing hemodialysis and after kidney transplantation

Research article

Professional dental prophylaxis increases salivary cortisol in children with dental behavioural management problems: a longitudinal study

Research article

Developing a model to assess community-level risk of oral diseases for planning public dental services in Australia

Research article

Factors associated with staying or leaving a dentist leader’s position – a qualitative study