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Tumor Necrosis factor a G-238A, G-308A and Tumor Necrosis factor b A329GThe two promoter polymorphisms in the Tumor Necrosis factor a gene are relatively frequent : G-238A is found in about 5 %, G-308A in about 30 % of caucasians, and both modulate in vitro production of Tumor Necrosis factor a by mononuclear cells (1). The Tumor Necrosis factor b A329G polymorphism, identical to the NcoI RFLP in intron 1, is even more common (40-45%). Clinically, these polymorphisms have so far been associated with survival of sepsis (2), various autoimmune diseases (6-10), atopy and asthma (3-5), hyperandrogenism (11), and the response to pathogens like hepatitits B and C virus and chlamydia trachomatis (12-16).Recently, TNF alpha polymorphisms have been implicated as modifiers of the phenotypic expression of hereditary haemochromatosis (17). References 1. Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism. Kaluza W et al. J Invest Dermatol 2000 Jun;114(6):1180-3 2. Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. Mira JP et al. JAMA 1999 Aug 11;282(6):561-8 3. Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients. Castro J et al. J Investig Allergol Clin Immunol 2000 May-Jun;10(3):149-54 4. Association between - 308 tumour necrosis factor promoter polymorphism and bronchial hyperreactivity in asthma. Li Kam Wa TC et al. Clin Exp Allergy 1999 Sep;29(9):1204-8 5. Association of a lymphotoxin alpha gene polymorphism and atopy in Italian families. Trabetti E et al. J Med Genet 1999 Apr;36(4):323-5 6. TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus. Rood MJ et al. Arthritis Rheum 2000 Jan;43(1):129-34 7. Decreased tumour necrosis factor-beta production in TNFB*2 homozygote: an important predisposing factor of lupus nephritis in Koreans Lee SH et al. Lupus 1997;6(7):603-9 8. The -308.1 polymorphism in the promoter region of the tumor necrosis factor gene is associated with ankylosing spondylitis independent of HLA-B27. McGarry F et al. J Rheumatol 1999 May;26(5):1110-6 9. TNF-238A promoter polymorphism contributes to susceptibility to ankylosing spondylitis in HLA-B27 negative patients. Gonzalez S et al. J Rheumatol 2001 Jun;28(6):1288-93 (PMID: 11409121) 10. TNFA and TNFB polymorphisms in myasthenia gravis. Skeie GO et al. Arch Neurol 1999 Apr;56(4):457-61 11. TNF-alpha and hyperandrogenism: a clinical, biochemical, and molecular genetic study. Escobar-Morreale HF et al. J Clin Endocrinol Metab 2001 Aug;86(8):3761-7 (PMID: 11502808) 12. Polymorphism in the promoter region of tumor necrosis factor-alpha gene is associated with severe meliodosis. Nuntayanuwat S et al. Hum Immunol 1999 Oct;60(10):979-83 13. A tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism is associated with chronic hepatitis B infection. Hohler T et al. Clin Exp Immunol 1998 Mar;111(3):579-82 14. Tumor necrosis factor alpha promoter polymorphism at position -238 is associated with chronic active hepatitis C infection. Hohler T et al. J Med Virol 1998 Mar;54(3):173-7 15. Donor polymorphism of tumor necrosis factor gene: relationship with variable severity of hepatitis C recurrence after liver transplantation. Rosen HR Transplantation 1999 Dec 27;68(12):1898-902 16. Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid. Conway DJ et al. Infect Immun 1997 Mar;65(3):1003-6 17.Tumor necrosis factor alpha promoter polymorphisms influence the phenotypic expression of hereditary hemochromatosis. Fargion S et al. Blood 2001 Jun 15;97(12):3707-12 (PMID: 11389006 ) |