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Genetic association of IFN-γ +874T/A polymorphism in Mexican patients with drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis

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Abstract

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, but potentially life-threatening diseases, characterized by widespread epidermal necrosis and are predominantly drug induced. There is a paucity of data regarding the role of cytokine and cytokine receptors polymorphisms in the pathoimmunology of SJS/TEN. The aim of this study was to investigate the role of TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg gene polymorphisms in SJS/TEN in Mexican Mestizo patients. Twenty-nine unrelated SJS/TEN patients and 128 unrelated healthy individuals were studied. Genomic extraction was carried out from complete blood samples using the salting out method. The PCR–RFLP method was used to amplify the following polymorphisms: TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg. TNF-α-308, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg polymorphisms were not associated with the genetic susceptibility to SJS/TEN. The distribution of TT, TA, AA genotypes of IFN-γ +874 was significantly different in SJS/TEN patients compared with controls (pC = 0.012). TA and AA genotypes were grouped to highlight the differences between patients and controls given by the absence of the AA genotype in the group of patients (pC = 0.03, OR = 3.61 95 % CI 1.20–11.6). This preliminary study suggests that IFN-γ +874 T/A polymorphism is associated with SJS/TEN.

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References

  1. Abe R, Shimizu T, Shibaki A, Nakamura H, Watanabe H, Shimizu H (2003) Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas ligand. Am J Pathol 162:1515–1520

    Article  PubMed  CAS  Google Scholar 

  2. Attwa E, El Sheikh AR (2006) Arg551 interleukin-4 receptor allele and atopic dermatitis. Egypt Dermatol Online J 2:2

    Google Scholar 

  3. Balding J, Kane D, Livingstone W et al (2003) Cytokine gene polymorphism association with psoriatic arthritis susceptibility and severity. Arthritis Rheum 48:1408–1423

    Article  PubMed  CAS  Google Scholar 

  4. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC (1993) Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 129:92–96

    Article  PubMed  CAS  Google Scholar 

  5. Behrendt C, Gollnick H, Bonnekoh B (2000) Up-regulated perforin expression of CD8 + blood lymphocytes in generalized non-anaphylactic drug eruptions and exacerbated psoriasis. Eur J Dermatol 10:365–369

    PubMed  CAS  Google Scholar 

  6. Borchers AT, Lee JL, Naguya SM, Cheema GS, Gershwin ME (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis. Autoimmun Rev 7:598–605

    Article  PubMed  CAS  Google Scholar 

  7. Caproni M, Torchia D, Schincaglia E et al (2006) Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis. Br J Dermatol 155:722–728

    Article  PubMed  CAS  Google Scholar 

  8. Charli-Joseph Y, Cruz-Fuentes C, Orozco-Topete R (2009) Incidence of adverse cutaneous drug reactions in a Mexican sample: an exploratory study on their association to tumour necrosis factor alpha TNF2 allele. J Eur Acad Dermatol Venereol 23:788–792

    Article  PubMed  CAS  Google Scholar 

  9. Chung WH, Hung SI, Hong HS et al (2004) Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428:486

    Article  PubMed  CAS  Google Scholar 

  10. Chung WH, Hung SI (2012) Recent advances in the genetics and immunology of Stevens-Johnson syndrome and toxic epidermal necrolysis. J Dermatol Sci 66:190–196

    Article  PubMed  CAS  Google Scholar 

  11. Genin E, Schumacher M, Roujeau J-C et al (2011) Genome-wide association study of Stenens-Johnson syndrome and toxic epidermal necrolysis in Europe. Orphanet J Rare Dis 6:52

    Article  PubMed  Google Scholar 

  12. Graves PE, Kebesch M, Halonen M et al (2000) A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children. J Allergy Clin Immunol 105:506–513

    Article  PubMed  CAS  Google Scholar 

  13. Hashemi M, Sharifi. Mood I, Nezamdoost M et al (2011) Functional polymorphism of interferon –γ (IFN-γ) gene +874T/A polymorphism is associated with pulmonary tuberculosis in Zahedan, southeast Iran. Prague Med Rep 112:38–43

    PubMed  CAS  Google Scholar 

  14. Hoffmann SC, Stanley EM, Cox D et al (2001) Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28- stimulated peripheral blood lymphocytes. Transplantation 72:1444–1450

    Article  PubMed  CAS  Google Scholar 

  15. Hung SI, Chung WH, Liou LB et al (2005) HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA 102:4134–4139

    Article  PubMed  CAS  Google Scholar 

  16. Juárez-Cedillo T, Zuñiga J, Acuña-Alonzo V et al (2008) Genetic admixture and diversity estimations in the Mexican Mestizo population from Mexico City using 15 STR polymorphic markers. Forensic Sci Int Genet 2:e37–e39

    Article  PubMed  Google Scholar 

  17. Lonjou C, Borot N, Sekula P et al (2008) European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 18:99–107

    Article  PubMed  CAS  Google Scholar 

  18. Lonjou C, Thomas L, Borot N et al (2006) A marker for Stevens-Johnson syndrome and toxic epidermal necrolysis: ethnicity matters. Pharmacogenomics J 6:265–268

    PubMed  CAS  Google Scholar 

  19. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  20. Nassif A, Moslehi H, Le Gouvello S et al (2004) Evaluation of the potential role of cytokines in toxic epidermal necrolisis. J Invest Dermatol 23:850–855

    Article  Google Scholar 

  21. Pichler WJ, Naisbitt DJ, Park BK (2010) Immune pathomechanism of drug hypersensitivity reactions. J Allergy Clin Immunol 127(3 Suppl.):S74–S81

    Google Scholar 

  22. Pirmohamed M, Friedmann PS, Molokhia M et al (2011) Phenotype standardization for immune-mediated drug-induced skin injury. Clin Pharmacol Ther 89:896–901

    Article  PubMed  CAS  Google Scholar 

  23. Pravica V, Perrey C, Stevens A, Lee J-H, Hutchinson IV (2000) A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Human Immunol 61:863–866

    Article  CAS  Google Scholar 

  24. Ueta M, Sotozano C, Inatomi T, Kojima K, Hamuro J, Kinoshita S (2008) Association of combined IL-13/IL-4R signaling pathway gene polymorphism with Stevens-Johnson syndrome accompanied by ocular surface complications. Invest Ophtalmol Vis Sci 49:1809–1813

    Article  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge Drs. Sagrario Hierro Orozco, Monserrat Solar Macías, Andrés Tirado Sánchez, Valeria Díaz Molina and Yadira Rodríguez Míguez MSc for their contribution in collecting blood samples for genomic screening.

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The authors declare no conflict of interest.

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Correspondence to Luis Llorente.

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Charli-Joseph, Y., Lima, G., Ramos-Bello, D. et al. Genetic association of IFN-γ +874T/A polymorphism in Mexican patients with drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Arch Dermatol Res 305, 353–357 (2013). https://doi.org/10.1007/s00403-012-1305-6

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  • DOI: https://doi.org/10.1007/s00403-012-1305-6

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