Türk Tüberküloz Hastalarında İnterferon Gamma IFN-g Promoter ve P2X7 Polimorfizimleri

Yıl 2016, Cilt: 2 Sayı: 3, 133 - 142, 01.01.2016

Esma Konuk Nilgün Sallakcı Olcay Yeğın

Öz

Dünya nüfusunun 1/3’ ü tüberküloz TB basili ile infektedir, fakat tüberküloz hastalığı bu bireylerin sadece % 5-10’ unda gelişmektedir. IFN-γ, TB hastalığına dirençte en önemli sitokindir. TB hastalığına yatkınlıkta “Purinergic Receptor” P2X7 ve IFNγ genlerindeki tek nükleotid değişimlerinin etkili olduğunu gösteren birçok yayın vardır. Araştırmalarımıza göre Türk toplumunda bu polimorfizmlerin etkisi ile ilişkili hiç çalışma yoktur. Bu projede biz TB hastalığına dirençte interferon gamma geni -155A/G ve -183G/T polimorfizmlerinin ilişkisini bir olgu - kontrol araştırması ile incelemeyi planladık. Aynı zamanda P2X7 geninde genellikle görülen A1513C polimorfizminide çalışmamızda araştırdık. Sonuçta TB hastalığında ve kontrol gruplarında IFNγ -155A/G ve -183G/T polimorfizmleri ile ilgili herhangi bir bulguya rastlanmadı. Bu sonuçlar bize bu polimorfizmin Türk toplumunda nadir olarak rastlanabileceğini gösteriyor. Bununla birlikte P2X7 genindeki Glu496Ala değişimine sebep olan A1513C polimorfizmi her iki grupta da belirlenmesine rağmen TB hastalığına yatkınlık ve dirençte bu hastalıkların görülmesi arasında anlamlı bir ilişki yoktur. AC; p=0,145 OR=1,521 CC; p=0,851 OR=1,114 AA; p=0,171 OR=1,447 . Bu bulgular da gösteriyor ki TB hastalığına yatkınlık genleri popülasyonlara göre farklılık gösterebilir

Anahtar Kelimeler

Tüberküloz, Interferon-Gamma, P2X7, Polymorfizim

Interferon Gamma IFN-γ Promoter and P2X7 Polymorphisms in Turkish Tuberculosis Patients

Öz

Almost one-third of the world population has been infected with the tuberculosis TB bacillus, but TB develops only in 5-10% of the infected people. IFN-γ interferon gamma is the most important cytokine that plays a role in resistance to TB. There are many studies demonstrating that a single nucleotide polymorphisms in the “Purinergic Receptor” P2X7 and promoter site of the IFN-γ genes may cause susceptibility to TB. To our knowledge, there is no study associated with the effects of these polymorphisms in the Turkish population. In this study, the relationship between -155A/G and -183G/T polymorphisms in the interferon gamma gene and susceptibility to TB disease were investigated in a case-control study. Also, the A1513C polymorphism that usually occurs in the P2X7 gene was examined in the same study. In conclusion, the -155A/G and -183G/T polymorphisms of the IFN-γ gene were not found in the TB patients and in the control groups. This outcome suggests us that these polymorphisms may barely appear in the Turkish population. However, although the P2X7 A1513C polymorphism that changes glutamine to alanine at codon 496 was detected in both groups, there was no significant relationship between the occurrence of this polymorphism and resistance/or susceptibility to TB AC; p=0.145 OR=1.521 CC; p=0.851 OR=1.114 AA; p=0.171 OR=1.447 .Our findings suggest that TB susceptibility genes may differ in different populations

Anahtar Kelimeler

Tuberculosis, Interferon-Gamma, P2X7, Polymorphism

Kaynakça

• Deligezer U, Akışık EE, Dalay N. The Application of the light cycler Fluorescence PCR in polymorphism analysis: Investigation of the Mthfr C677T Polymorphism in childhood and adult patients with Myeloid Leukemia. Türk Onkoloji Dergisi 2004; 19:134-9.
• Casanova JL, Abel L. Genetic dissection of immunity to mycobacteria: The human model. Annu Rev Immunol 2002; 20:581-620.
• Cooke GS, Hill AV. Genetics of susceptibility to human infectious disease. Nat Rev Genet 2001; 2:967-77.
• Barnes PF, Cave MD. Molecular epidemiology of tuberculosis. N Engl J Med 2003; 349:1149-56.
• Narayanan S. Molecular epidemiology of tuberculosis. Indian J Med Res 2004; 120:233-47.
• Surprenant A, Rassendren F, Kawashima E, North RA, Buell G. The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 1996; 272: 735-8.
• Berrington WR, Hawn TR. Mycobacterium tuberculosis, macrophages, and the innate immune response: Does common variation matter? Immunol Rev 2007; 219:167- 86.
• Fernando SL, Saunders BM, Sluyter R, Skarratt KK, Wiley JS, Britton WJ. Gene dosage determines the negative effects of polymorphic alleles of the P2X7 receptor on adenosine triphosphate-mediated killing of mycobacteria by human macrophages. J Infect Dis 2005; 192:149-55.
• Shemon AN, Sluyter R, Fernando SL, Clarke AL, Dao- Ung LP, Skarratt KK, Saunders BM, Tan KS, Gu BJ, Fuller SJ, Britton WJ, Petrou S, Wiley JS. A Thr357 to Ser polymorphism in homozygous and compound heterozygous subjects causes absent or reduced P2X7 function and impairs ATP-induced mycobacterial killing by macrophages. J Biol Chem 2006; 281:2079-86.
• Li CM, Campbell SJ, Kumararatne DS, Bellamy R, Ruwende C, McAdam KP, Hill AV, Lammas DA. Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population. J Infect Dis 2002; 186:1458-62.
• Fernando SL, Saunders BM, Sluyter R, Skarratt KK, Goldberg H, Marks GB, Wiley JS, Britton WJ. A polymorphism in the P2X7 gene increases susceptibility to extrapulmonary tuberculosis. Am J Respir Crit Care Med 2007; 175: 360-6.
• Saunders BM, Fernando SL, Sluyter R, Britton WJ, Wiley JS. A loss-of-function polymorphism in the human P2X7 receptor abolishes ATP-mediated killing of mycobacteria. J Immunol 2003; 171:5442-6.
• Organization WH. Global tuberculosis control. WHO report Geneva, Switzerland, 1999; WHO/CDS/CPS/ TB 99.259. http://www.who.int/en/
• Gaudelus J, De Pontual L. Epidemiology of tuberculosis in France. Arch Podiatry 2005; 12:83-7.
• Kochi A. Tuberculosis: distribution, risck factors, mortality. Immunobiology 1994; 191:325-36.
• Rassendren F, Buell GN, Virginio C, Collo G, North RA, Surprenant A. The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA. J Biol Chem 1997; 272:5482-6.
• Gu BJ, Zhang W, Worthington RA, Sluyter R, Dao- Ung P, Petrou S, Barden JA, Wiley JS. A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. J Biol Chem 2001; 276:11135-42.
• Wiley JS, Gargett CE, Zhang W, Snook MB, Jamieson GP. Partial agonists and antagonists reveal a second permeability state of human lymphocyte P2Z/P2X7 channel. Am J Physiol 1998; 275:C1224-31.
• Humphreys BD, Rice J, Kertesy SB, Dubyak GR. Stress- activated protein kinase/JNK activation and apoptotic induction by the macrophage P2X7 nucleotide receptor. J Biol Chem 2000; 275:26792-8.
• Boldt W, Klapperstuck M, Buttner C, Sadtler S, Schmalzing G, Markwardt F. Glu496Ala polymorphism of human P2X7 receptor does not affect its electrophysiological phenotype. Am J Physiol Cell Physiol 2003; 284:C749-56.
• Bream JH, Ping A, Zhang X, Winkler C, Young HA. A single nucleotide polymorphism in the proximal IFN- gamma promoter alters control of gene transcription. Genes Immun 2002; 3:165-9.
• Chevillard C, Henri S, Stefani F, Parzy D, Dessein A. Two new polymorphisms in the human interferon gamma (IFN-gamma) promoter. Eur J Immunogenet 2002; 29: 53-6.
• Sallakci N, Coskun M, Berber Z, Gurkan F, Kocamaz H, Uysal G, Bhuju S, Yavuzer U, Singh M, Yegin O. Inter- feron-gamma gene+874T-A polymorphism is associated with tuberculosis and gamma interferon response. Tuber- culosis (Edinb) 2007; 87:225-30.
• Qi S, Cao B, Jiang M, Xu C, Dai Y, Li K, Wang K, Ke Y, Ning T. Association of the -183 polymorphism in the IFN- gamma gene promoter with hepatitis B virus infection in the Chinese population. J Clin Lab Anal 2005; 19:276-81.
• Sluyter R, Dalitz JG, Wiley JS. P2X7 receptor polymor- phism impairs extracellular adenosine 5’-triphosphate- induced interleukin-18 release from human monocytes. Genes Immun 2004; 5:588-91.
• Sluyter R, Shemon AN, Wiley JS. Glu496 to Ala polymorphism in the P2X7 receptor impairs ATP- induced IL-1 beta release from human monocytes. J Immunol 2004; 172:3399-405.
• Georgiou JG, Skarratt KK, Fuller SJ, Martin CJ, Christopherson RI, Wiley JS, Sluyter R. Human epidermal and monocyte-derived langerhans cells express functional P2X receptors. J Invest Dermatol 2005; 125: 482-90.
• Sluyter R, Wiley JS. Extracellular adenosine 5’-triphos- phate induces a loss of CD23 from human dendritic cells via activation of P2X7 receptors. Int Immunol 2002; 14:1415-21.
• Gu BJ, Wiley JS. Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor. Blood 2006; 107:4946-53.
• Bai J, Marks GB, Stewart GJ, Simpson SE, Sullivan EA. Specificity of notification for tuberculosis among screened refugees in NSW. Aust N Z J Public Health 1999; 23: 410- 3.
• Hoal-Van Helden EG, Epstein J, Victor TC, Hon D, Lewis LA, Beyers N, Zurakowski D, Ezekowitz AB, Van Helden PD. Mannose-binding protein B allele confers protection against tuberculous meningitis. Pediatr Res 1999; 45:459- 64.
• Kim JH, Lee SY, Lee SH, Sin C, Shim JJ, In KH, Yoo SH, Kang KH. NRAMP1 genetic polymorphisms as a risk factor of tuberculous pleurisy. Int J Tuberc Lung Dis 2003; 7:370-5.
• Nino-Moreno P, Portales-Perez D, Hernandez-Castro B, Portales-Cervantes L, Flores-Meraz V, Baranda L, Gomez-Gomez A, Acuna-Alonzo V, Granados J, Gonzalez-Amaro R. P2X7 and NRAMP1/SLC11 A1 gene polymorphisms in Mexican mestizo patients with pulmonary tuberculosis. Clin Exp Immunol 2007; 148: 469-77.
• Kusner DJ, Adams J. ATP-induced killing of virulent Mycobacterium tuberculosis within human macrophages requires phospholipase D. J Immunol 2000; 164:379-88.
• Mokrousov I, Sapozhnikova N, Narvskaya O. Mycobacterium tuberculosis co-existence with humans: Making an imprint on the macrophage P2X(7) receptor gene? J Med Microbiol 2008; 57:581-4.