Skip to main content

TNF-α-308 promoter G/A and PTPN22 (1858 C/T) genes polymorphisms in Egyptian patients with systemic lupus erythematosus

Abstract

Tumor necrosis factor alpha (TNF-α) promoter gene polymorphism at position 308 and that of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) at position 1858 C/T have been inconsistently implicated as genetic risk factors for systemic lupus erythematosus (SLE) in some populations. We investigated the possible association of these polymorphisms with SLE susceptibility, and whether serum TNF-α level is related to different genotypes and disease activity in Egyptian SLE patients. TNF-α-308 G/A and PTPN22 C1858T polymorphisms were determined by PCR-restriction fragment length polymorphism analysis in 40 SLE patients and 40 unrelated healthy controls. Serum TNF-α level was measured by ELISA method. The median serum TNF-α was significantly higher in SLE patients than in controls (P < 0.001). A significant positive correlation was detected between serum TNF-α and SLE activity index (r = 0.723, P < 0.001). There was no significant difference in TNF-α-308 G/A genotypes or allele frequency between SLE cases and controls (P = 0.108 and P = 0.133, respectively). Diabetes was the only clinical feature in SLE patients that showed significant higher frequency with GA genotype than with GG genotype (P = 0.001). Risk estimation for the TNF-α-308 genotypes was of no significant (odds ratio = 2.429; 95 % CI = 0.8–7.2; P = 0.108). Concerning PTPN22 1858 C/T, there was no significant difference in PTPN22 C/T genotypes or allele frequency between SLE cases and controls (P = 0.152 and P = 0.155, respectively). TNF-α-308 G/A and PTPN22 (1858 C/T) polymorphisms do not exhibit a significant influence on the susceptibility of SLE in Egyptian patients. However, serum TNF-α level could be a sensitive marker of SLE disease activity.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  • Aksoy R, Duman T, Keskin O, Düzgün N (2011) No association of PTPN22 R620 W gene polymorphism with rheumatic heart disease and systemic lupus erythematosus. Mol Biol Rep 38(8):5393–5396

    PubMed  Article  CAS  Google Scholar 

  • Al-Mutairi S, Al-Awadhi A, Raghupathy et al (2007) Lupus patients with pulmonary involvement have a pro-inflammatory cytokines profile. Rheumatol Int 27:621–630

    PubMed  Article  CAS  Google Scholar 

  • Azizah MR, Kuak SH, Ainol SS, Rahim MN, Normaznah Y, Norella K (2004) Association of TNF-α promoter gene polymorphism with susceptibility and clinical-immunological findings of SLE. Asian Pacific Journal of Allergy and Immunology 22:159–163

    PubMed  CAS  Google Scholar 

  • Bonavida B (1991) Immunomodulatory effect of tumor necrosis factor. Biotherapy 3:127–133

    PubMed  Article  CAS  Google Scholar 

  • D'Alfonso S, Colombo G, Della Bella S, Scorza R, Momigliano-Richiardi P (1996) Association between polymorphisms in the TNF region and systemic lupus erythematosus in the Italian population. Tissue Antigens 47:551–555

    PubMed  Article  Google Scholar 

  • Eliopoulos E, Zervou MI, Andreou A, Dimopoulou K, Cosmidis N, Voloudakis G, Mysirlaki H, Vazgiourakis V, Sidiropoulos P, Niewold TB, Boumpas DT, Goulielmos GN (2011) Association of the PTPN22 R620W polymorphism with increased risk for SLE in the genetically homogeneous population of Crete. Lupus 20(5):501–506

    PubMed  Article  CAS  Google Scholar 

  • Esposito P, Balletta MM, Procino A, Postiglione L, Memoli B (2009) Interleukin-6 release from peripheral mononuclear cells is associated to disease activity and treatment response in patients with lupus nephritis. Lupus 18(14):1329–1330

    Google Scholar 

  • Fugger L, Morling N, Ryder LP, Georgsen J, Jakobsen BK, Svejgaard A et al (1989) NcoI restriction fragment length polymorphism (RFLP) of the tumor necrosis factor (TNF alpha) region in four autoimmune diseases. Tissue Antigens 34:17–22

    PubMed  Article  CAS  Google Scholar 

  • Gabay C, Cakir N, Moral F, Roux-Lombard P, Meyer O, Dayer JM et al (1997) Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. J Rheumatol 24:303–308

    PubMed  CAS  Google Scholar 

  • Garnacho MJ, Aldabo PT, Garnacho MC, Cayuela A, Jiménez R, Barroso S, Ortiz-Leyba C (2006) Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis. Crit Care 10(4):111

    Article  Google Scholar 

  • Gomez LM, Anaya JM, Gonzalez CI, Pineda-Tamayo R, Otero W, Arango A, Martín J (2005) PTPN22 C1858T polymorphism in Colombian patients with autoimmune diseases. Genes and Immunity 6:628–631

    PubMed  Article  CAS  Google Scholar 

  • Goronzy JJ, Weyand CM (2004) T-cell regulation in rheumatoid arthritis. Curr Opin Rheumatol 16:212–217

    PubMed  Article  CAS  Google Scholar 

  • Gregersen PK, Lee HS, Batliwalla F, Begovich AB (2006) PTPN22: setting thresholds for autoimmunity. Semin Immunol 18(4):214–223

    PubMed  Article  CAS  Google Scholar 

  • Guarnizo ZP, Lopez Y, Giraldo M, Garcia N, Rodriguez L, Ramirez L, Uribe O, Garcia L, Vasquez G (2007) Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens 70(5):376–382

    Article  Google Scholar 

  • Hirankarn N, Avihingsanon Y, Wongpiyabovorn J (2007) Genetic susceptibility to SLE is associated with TNF-alpha gene polymorphism −863, but not −308 and −238, in Thai population. Int J Immunogenet 34(6):425–430

    PubMed  Article  CAS  Google Scholar 

  • Jawaheer D, Seldin MF, Amos CI, Chen WV, Shigeta R, Etzel C et al (2003) Screening the genome for rheumatoid arthritis susceptibility genes: a replication study and combined analysis of 512 multicase families. Arthritis Rheum 48:906–916

    PubMed  Article  CAS  Google Scholar 

  • Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C et al (2004) Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 75:504–507

    PubMed  Article  CAS  Google Scholar 

  • Lee YH, Harley JB, Nath SK (2006) Meta-analysis of TNF-alpha promoter −308 A/G polymorphism and SLE susceptibility. Eur J Hum Genet 14:364–371

    PubMed  Article  CAS  Google Scholar 

  • Lin YJ, Chen RH, Wan L, Sheu JC et al (2009) Association of TNF-alpha gene polymorphisms with systemic lupus erythematosus in Taiwanese patients. Lupus 18:974–979

    PubMed  Article  Google Scholar 

  • Mahmoud RA, El-Gendi HI, Ahmed HH (2005) Serum neopterin, tumor necrosis factor-alpha and soluble tumor necrosis factor receptor II (p75) levels and disease activity in Egyptian female patients with systemic lupus erythematosus. Clin Biochem 38(2):134–141

    PubMed  Article  CAS  Google Scholar 

  • Mosca M, Bombardieri S (2006) Assessing remission in systemic lupus erythematosus. Clin Exp Rheumatol 24(43):100–104

    Google Scholar 

  • Orozco G, Sánchez E, González-Gay MA, López-Nevot MA, Torres B, Cáliz R et al (2005) Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Rheum 52(1):219–224

    PubMed  Article  CAS  Google Scholar 

  • Parks CG, Pandey JP, Dooley MA, Treadwell EL, St Clair EW, Gilkeson GS et al (2004) Genetic polymorphisms in tumor necrosis factor (TNF)-alpha and TNF-beta in a population-based study of systemic lupus erythematosus: associations and interaction with the interleukin-1alpha-889 C/T polymorphism. Hum Immunol 65:622–631

    PubMed  Article  CAS  Google Scholar 

  • Pradhan V, Borse V, Ghosh K (2010) PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility. J Postgrad Med 56(3):239–242

    PubMed  Article  CAS  Google Scholar 

  • Reddy MV, Johansson M, Sturfelt G, Jönsen A, Gunnarsson I, Svenungsson E et al (2005) The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1. Genes Immun 6:658–662

    PubMed  CAS  Google Scholar 

  • Rudwaleit M, Tikly M, Khamashta M, Gibson K, Klinke J, Hughes G et al (1996) Interethnic differences in the association of tumor necrosis factor promoter polymorphisms with systemic lupus erythematosus. J Rheumatol 23:1725–1728

    PubMed  CAS  Google Scholar 

  • Sabry A, Sheashaa H, El-Husseini A, Mahmoud K, Eldahshan KF, George SK, Abdel-Khalek E, El-Shafey EM, Abo-Zenah H (2006) Proinflammatory cytokines (TNF-alpha and IL-6) in Egyptian patients with SLE: its correlation with disease activity. Cytokine 35:148–153

    PubMed  Article  CAS  Google Scholar 

  • Santos MJ, Carmona-Fernandes D, Caetano-Lopes J, Perpétuo IP, Vidal B, Capela S et al (2011) TNF promoter −308 G > A and LTA 252 A > G polymorphisms in Portuguese patients with systemic lupus erythematosus. Rheumatol Int Clin Exp Invest 10:1950–1957

    Google Scholar 

  • Serrano NC, Millan P, Paez MC (2006) Non-HLA associations with autoimmune diseases. Autoimmun Rev 5:209–214

    PubMed  Article  CAS  Google Scholar 

  • Steck AK, Liu SY, McFann K, Barriga KJ, Babu SR, Eisenbarth GS, Rewers MJ, She JX (2006) Association of the PTPN22/LYP gene with type 1 diabetes. Pediatr Diabetes 7:274–278

    PubMed  Article  Google Scholar 

  • Takeuchi F, Nakano K, Nabeta H, Hong GH, Kawasugi K, Mori M et al (2005) Genetic contribution of the tumour necrosis factor (TNF) B + 252*2/2 genotype, but not the TNFa, b microsatellite alleles, to systemic lupus erythematosus in Japanese patients. Int J Immunogenet 32:173–178

    PubMed  Article  CAS  Google Scholar 

  • Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    PubMed  Article  CAS  Google Scholar 

  • Tobón GJ, Correa PA, Gomez LM, Anaya JM (2005) Lack of association between TNF-308 polymorphism and the clinical and immunological characteristics of systemic lupus erythematosus and primary Sjögren's syndrome. Clin Exp Rheumatol 23(3):339–344

    PubMed  Google Scholar 

  • Viken MK, Amundsen SS, Kvien TK, Boberg KM, Gilboe IM, Lilleby V, Sollid LM, Forre OT, Thorsby E, Smerdel A, Lie BA (2005) Association analysis of the 1858 C > T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases. Genes Immun 6:271–273

    PubMed  Article  CAS  Google Scholar 

  • Wu H, Cantor RM, Graham DS, Lingren CM, Farwell L, Jager PL, Bottini N, Grossman JM, Wallace DJ, Hahn BH, Julkunen H, Hebert LA, Rovin BH et al (2005) Association analysis of the R620W polymorphism of protein tyrosine phosphatase PTPN22 in systemic lupus erythematosus families: increased T allele frequency in systemic lupus erythematosus patients with autoimmune thyroid disease. Arthritis Rheum 52:2396–2402

    PubMed  Article  CAS  Google Scholar 

  • Zou YF, Feng XL, Tao JH, Su H, Pan FM, Liao FF, Ye F, Ye DQ (2010) Meta-analysis of TNF-α promoter -308A/G polymorphism and SLE susceptibility in Asian populations. Rheumatol Int 31(8):1055–1064

    PubMed  Article  Google Scholar 

  • Zúñiga J, Vargas-Alarcón G, Hernández-Pacheco G, Portal-Celhay C, Yamamoto-Furusho JK, Granados J (2001) Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with systemic lupus erythematosus (SLE). Genes Immun 2:363–366

    PubMed  Article  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mona Mohamad Fathy.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fathy, M.M., Kamal, M.M., El-Mougy, F. et al. TNF-α-308 promoter G/A and PTPN22 (1858 C/T) genes polymorphisms in Egyptian patients with systemic lupus erythematosus. Comp Clin Pathol 22, 947–954 (2013). https://doi.org/10.1007/s00580-012-1506-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-012-1506-6

Keywords

  • Systemic lupus erythematosus
  • TNF-α-308 G/A polymorphism
  • PTPN22 1858 C/T polymorphism