CLINICAL IMMUNOLOGY
Tumour necrosis factor gene polymorphisms in Egyptian patients with rheumatoid arthritis and their relation to disease activity and severity
 
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1
Department of Clinical Pathology, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt
 
2
Department of Rheumatology and Rehabilitation, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt
 
 
Submission date: 2016-12-03
 
 
Final revision date: 2017-01-22
 
 
Acceptance date: 2017-01-24
 
 
Publication date: 2019-09-30
 
 
Cent Eur J Immunol 2019;44(3):277-284
 
KEYWORDS
ABSTRACT
Aim of the study:
The present case control study was conducted to assess the association of LTA 252 A>G, TNF-α 308 G>A, and TNF-α 1031 T>C gene polymorphisms with rheumatoid arthritis (RA), and their involvement in disease activity and severity.

Material and methods:
A total of 70 Egyptians, including 35 RA patients and 35 healthy control individuals, were included in the study. The RA patients comprised 34 females and one male. Cases with RA were diagnosed by a rheumatologist and fulfilled the 2010 ACR/EULAR criteria. Modified disease activity score (DAS28) was used to assess disease activity. Van Der Heijde-modified Sharp score (vdHSS) was used to assess radiological changes for assessment of disease severity. PCR-RFLP was used to detect the association of LTA 252 A>G, TNF-α 308 G>A, and TNF-α 1031 T>C gene polymorphisms with RA.

Results:
TNF-α 308 G allele and TNF-α 308 GG genotype were significantly higher in RA patients compared to healthy control subjects (p = 0.04 and p = 0.001, respectively). TNF-α 308 G allele and GG genotype were significantly higher in the RA non-remission group compared to the remission group (p = 0.008, p < 0.001). Patients with the TNF-α 308 AG genotype had higher mean of Sharp score compared to the patients with the GG and AA genotypes (p = 0.007). There was no significant association between LTA 252 A>G and TNF-α 1031 T>C gene polymorphisms and RA.

Conclusions:
Our results suggest that TNF-α 308 G/A gene polymorphism is genetically associated with RA and involved in disease activity and severity in Egyptian patients.
REFERENCES (49)
1.
Raina P, Matha Roo K, Kumar A, et al. (2014): Association of TNF-Alpha-308 G>A polymorphism with rheumatoid arthritis in two north Indian cohorts. Arch Rheumatol 29; 421-249.
 
2.
Goldsby RA, Kindt TJ, Osborne BA (2006): Kuby Immunology, 6th ed. W.H. Freeman & Company, New York.
 
3.
Mateen S, Zafar A, Moin S, et al. (2016): Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clinica Chemica Acta 455: 161-171.
 
4.
Chen R, Fang M, Cai Q, et al. (2007): Tumor necrosis factor alpha-308 polymorphism is associated with rheumatoid arthritis in Han population of Eastern China. Rheumatol Int 28: 121-126.
 
5.
Firestein GS (2003): Evolving concepts of rheumatoid arthritis. Nature 423: 356-361.
 
6.
Gambhir D, Lawrence A, Aggarwal A, et al. (2010): Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int 30; 1211-1217.
 
7.
Brennan FM, Maini RN, Feldmann M (1992): TNF alpha – a pivotal role in rheumatoid arthritis? Br J Rheumatol 31: 293-298.
 
8.
Feldmann M, Brennan FM, Foxwell BM, Mainin RN (2001): The role of TNF alpha and IL-1 in rheumatoid arthritis. Curr Dir Autoimmun 3: 188-199.
 
9.
Beutler B, Cerami A (1989): The biology of cachectin/TNF-α primary mediator of the host response. Annu Rev Immunol 7: 625-655.
 
10.
Nedwin GE, Svedersky LP, Bringman TS, et al. (1985): Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol 135: 2492-2497.
 
11.
Hohmann HP, Remy R, Brockhaus M, van Loon AP (1989): Two different cell types have different major receptors for human tumor necrosis factor (TNF alpha). J Biol Chem 264: 14927-14934.
 
12.
Bradley JR (2008): TNF-mediated inflammatory disease. J Pathol 214: 149-160.
 
13.
Hehlgans T, Pfeffer K (2005): The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115: 1-20.
 
14.
Lee YH, Bae SC (2015): Association between TNF- polymorphisms and susceptibility to rheumatoid arthritis and vitiligo. A meta-analysis. Genet Mol Res 14: 5548-5599.
 
15.
Thomson WM, Edwards SJ, Dobson-Le DP, et al. (2001): IL-1 genotype and adult periodontitis among young New Zealanders. J Dent Res 80: 1700-1703.
 
16.
Aringer M, Smolen JS (2003): SLE – Complex cytokine effects in a complex autoimmune disease: tumor necrosis factor in systemic lupus erythematosus. Arthritis Res Ther 5: 172-177.
 
17.
Khanna D, Wu H, Park G, et al. (2006): Association of tumor necrosis factor  polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort. Arthritis and Rheum 54: 1105-1116.
 
18.
Panoulas VF, Nikas SN, Smith JP, et al. (2008): Lymphotoxin 252A/G polymorphism is commonly associated with myocardial infarction in patients with rheumatoid arthritis. Ann Rheum Dis 67: 1550-1556.
 
19.
Boraska V, Zeggini E, Groves CJ, et al. (2009): Family-based analysis of tumor necrosis factor and lymphotoxinalpha tag polymorphism with type 1 diabetes in the population of South Croatia. Hum Immunol 70: 195-199.
 
20.
Messer G, Spengler U, Jung MC, et al. (1991): Polymorphic structure of the tumor necrosis factor (TNF) locus: an Ncol polymorphism in the first intron of the human TNF-βeta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-βeta production. J Exp Med 173: 209-219.
 
21.
Abraham LJ, French MAH, Dawkins RL (1993): Polymorphic MHC ancestral haplotypes affect the activity of tumor necrosis factor alpha. Clin Exp Immunol 92: 14-18.
 
22.
Takeuchi F, Nabeta H, Hong GH, et al. (2005): The genetic contribution of the TNFα11 microsatellite allele and the TNFβ + 252*2 allele in Japanese RA. Clin Exp Rheumatol 23: 494-498.
 
23.
Aletaha D, Neogi TT, Silman AJ (2010): 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69: 1580-1588.
 
24.
Villaverde V, Balsa A, Cantalejo M, et al. (2000): Activity indices in rheumatoid arthritis. J Rheumatol 27: 2576-2581.
 
25.
Van der Heijde DM (1999): How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 26: 743-745.
 
26.
Avise JC (1994): Molecular markers, natural history and evolution. Chapman and Hall, New York: 511.
 
27.
Karray EF, Bendhifallah I, BenAbdelghani K, et al. (2011): Tumor necrosis factor gene polymorphisms and susceptibility to rheumatoid arthritis in regional Tunisian population. J Infect Dis Immun 3: 30-35.
 
28.
Bonyadi M, Jahanafrooz Z, Esmaeili M, et al. (2009): TNF- gene polymorphisms in Iranian Azeri Turkish patients with Behcet’s Disease. Rheumatol Int 30: 285-289.
 
29.
Cabrara M, Shaw MA, Sharples C, et al. (1995): Polymorphism in Tumor Necrosis Factor Genes Associated with Mucocutaneous Leishmaniasis. Exp Med 182: 1259-1264.
 
30.
Reveille JD (1998): The genetic contribution to the pathogenesis of rheumatoid arthritis. Curr Opin Rheumatol 10: 187-200.
 
31.
van der Woude D, Houwing-Duistermaat JJ, Toes RE, et al. (2009): Quantitative heritability of anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis. Arthritis Rheum 60: 916-923.
 
32.
Orozco G, Eyre S, Hinks A, et al. (2010): Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study. Ann Rheum Dis 69: 813-816.
 
33.
Hussein YM, El-Shal AS, Rezk NA, et al. (2013): Influence of interleukin-4 gene polymorphisms and interleukin-4 serum level on susceptibility and severity of rheumatoid arthritis in Egyptian population. Cytokine 61: 849-855.
 
34.
Sharma S, Ghosh B, Sharma SK (2008): Association of TNF polymorphisms with sarcoidosis, its prognosis and tumour necrosis factor (TNF)-alpha levels in Asian Indians. Clin Exp Immunol 151: 251-259.
 
35.
Mosaad YM, Abdelsalam A, El-Bassiony SR (2011): Association of tumour necrosis factor-alpha-308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis. Int J Immunogenet 38: 427-433.
 
36.
Balog A, Gal J, Gyulai Z, et al. (2004): Tumor necrosis factor-alpha and heat-shock protein 70-2 gene polymorphisms in a family with rheumatoid arthritis. Acta Microbiol Immunol Hung 51: 263-269.
 
37.
Al-Rayes H, Al-Swailem R, Albelawi M, et al. (2011): TNF- and TNF- gene polymorphism in Saudi rheumatoid arthritis patients. Clin Med Insights Arthritis Musculoskelet Disord 4: 55-63.
 
38.
Nemec P, Pavkova-Goldbergova M, Stouracova M, et al. (2008): Polymorphism in the tumor necrosis factor- gene promoter is associated with severity of rheumatoid arthritis in the Czech population. Clin Rheumatol 27: 59-65.
 
39.
Ursum J, van der Weijden MA, van Schaardenburg D, et al. (2010): IL10 GGC haplotype is positively and HLA-DQA1*05-DQB1*02 is negatively associated with radiographic progression in undifferentiated arthritis. J Rheumatol 37: 1431-1438.
 
40.
Stojanović S, Jevtović-Stoimenov T, Stanković A, et al. (2011): Association of TNF-αlpha polymorphism (-308 A/G) with high activity of rheumatoid arthritis and therapy response to Etanercept. Srp Arh Celok Lek 139: 784-789.
 
41.
Lee YH, Ji JD, Song GG (2007): Tumor necrosis factor- promoter -308 A/G polymorphism and rheumatoid arthritis susceptibility: a meta-analysis. J Rheumatol 34: 43-49.
 
42.
Reneses S, González-Escribano MF, Fernández-Suárez A, et al. (2009): The value of HLA-DRB1 shared epitope, -308 tumor necrosis factor-alpha gene promoter polymorphism, rheumatoid factor, anti-citrullinated peptide antibodies, and early erosions for predicting radiological outcome in recent-onset rheumatoid arthritis. J Rheumatol 36: 1143-1149.
 
43.
Zake LN, Cimdina I, Rumba I, et al. (2002): Major histocompatibility complex class I chain related (MIC) A gene, TNFα microsatellite alleles and TNFB alleles in juvenile idiopathic arthritis patients from Latvia. Hum Immunol 63: 418-423.
 
44.
Santos MJ, Fernandes D, Caetano-Lopes J, et al. (2011): Lymphotoxin- 252 A>G polymorphism: a link between disease susceptibility and dyslipidemia in rheumatoid arthritis? J Rheumatol 38: 1244-1249.
 
45.
Grabar PB, Logar D, Tomšič M, et al. (2009): Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients. Dis Markers 26: 41-48.
 
46.
Hajeer AH, Hutchinson IV (2001): Influence of TNF alpha gene polymorphisms on TNF alpha production and disease. Hum Immunol 62: 1191-1199.
 
47.
Rezaieyazdi Z, Afshari JT, Sandooghi M, Mohajer F (2007): Tumor necrosis factor -308 promoter polymorphism in patients with rheumatoid arthritis. Rheumatol Int 28: 189-191.
 
48.
Barton A, Platt H, Salway F (2004): Polymorphism in the tumour necrosis factor gene are not associated with severity of inflammatory polyarthritis. Ann Rheum Dis 63: 280-284.
 
49.
Ates O, Hatem G, Hamuryudan V, Topal-Sarikaya A (2008): Tumor necrosis factor-alpha and interleukin-10 gene promoter polymorphism in Turkish rheumatoid arthritis patients. Clin Rheumatol 27: 1243-1248.
 
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