Lack of association of 1513 a/c polymorp hism in p2x, gene with susceptibility to pulmonary and extrap ulmonary tubercu losisul
Giriş : Latent, pulmoner ve ekstrapulmoner şeklin de farklı klinik formları olan tüberküloz, dünya genelin de ölüme sebebiyet verenh astalıkların en önemlilerin den biridir. Aday gen lerle yapılan ça lışmalarda yaygın polimorfizmlerin tüberkülozun gelişmesin de etkiliolabilece ği sonucuna varılmıştır. Bu ça lışmada P2X7 genindeki 1513 A/C polimorfizminin tüberkülozun etyopatogenezisindeki rolü-7nün ortaya çıkarılmas ı amaçlanmıştır.Materya l ve Metod: Bu çalışma 160 tüberkülozlu (71 pulmoner tüberküloz lu ve 89 ekstrapulmoner tüberkülozlu) 160 da sa ğlıklıbireyi kapsama ktadır. Genomik DNA izolasyonu gerçekleştirildikten sonra P2X7 genindeki 1513 A/C polimorfizmi PCR-RFLP meto-7duyla genotiplen dirildi.Bulg ular: AA genotipinin fre kansı kontrol grubun da %47.5, hastalarda %56.87, AC genotipinin fre kansı kontrol grubun da %39.37,h astalarda %32.5, CC genotipinin frekansı kontrol grubun da %13.12, h astalarda %10.62 olarak saptan dı. Hasta lar ile kontrol gru-bunun allel ve genotip frekansları aras ında anlamlı bir farklılık bulunamadı.Sonuç: Sonuçlarımız Türkiyenin doğu bölgesin de P2X7 genindeki, 1513 A/C polimorfizminin pulmoner ve ekstrapulmoner tüberkü-7loz h astalı ğıyla ilişkisinin olmadı ğın ı gösterdi.
Pulmoner ve ekstrapulmoner tüberkülozlu hastalarda p2 x, genindeki 1513 a/c polimorfizmin hastalıkla ilişkisinin olmaması
In troductio n : Tu b ercu losis, is one of th e a lea din g causes of death worldwide, is c h aracterize d b y different c linica l forms inclu ddin g: dlatent, localized pulmonary infection and extrapulmonary tuberculosis. Candidate gene association studies have implicated co m m onmmpo lymoph isms in genes th at may influence th e deve lopment of tu b ercu losis. T h is stu dy, aime d to e lucidate th e ro le of P2X7 ge n e in n71513A/C polymorphism the etiopatho genesis of tuberculosis.M ate rials a n d Meth ods: T h e stu dy inc lu de d 160 patients with tu b ercu losis (71 pu lmonary an d 89 extra pu lmonary tu b ercu losis) an d)160 health y controls. Genomic DNA was isolated and 1513A/C polymorphism in P2 X7 gene was genotyped by PCR-RFLP method. Results: Fre q uenc y o f P2 X7 AA genotype was 47.5% in controls 7an d 56.87% in patients, AC fre q uenc y was 39.37% contro ls an d32.5% in patients, CC genotype was 13.12% in contro ls an d10.62% in patients. No significant difference in a lle le an d geno -type fre q uencies (1513A/C polymorphism) between tuberculosispatients an d contro ls was found.
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- 1. Cooke GS, Hill AV. Genetics of susce ptibility to human infectious disease. Nat Rev Genet 2001 ;2:967-77.
- 2. Barnes DS. Historical perspectives on th e etiology of tuber- culosis. Microbes Infect 2000;2:431-40.
- 3. Ben-Se lma W, Harizi H, Bougmiza I, Hannach i N, Kahla IB, Zaieni & Boukadida J. Interferon gamma +874 T/A polymor phism is associated with susce ptibility to active pulmonary tuberculosis development in Tunisian patients. DNA Cell Biol 2011 ;2011:379-87. DOI: 10.1089/ dna.2010.1157.
- 4. Döffin ger R, Dupuis S, Picard C, Fiesch i C, Fein ber g J, Barcenas- Morales G & Casanova JL. In h erited disorders of IL-12- and IFN gamma-mediated immunity: a molecular genetics update. Mol Immunol 2001;38:903-9.
- 5. Bellamy R. Susce ptibility to mycobacterial infections: the importance of h ost genetics. Genes Immun 2003;4:4-11 .
- 6. Buell GN , Talabot F, Gos A, Lorenz J, Lai E, Morris MA & Antonarakis S E. Gene structure an d c h romosomal localiza - tion of th e huma n P2X7 receptor. Receptor Channel 7 1998;5:347-54.
- 7. Fernando SL, Saun ders BM, Sluyter R, S karratt KK, Wiley JS & Britton WJ. Gene dosa ge determines th e ne gative effects of polymor ph ic alleles of th e P2 X7 receptor on adenosine7 triph osph ate-me diated killin g of mycobacteria by h uman macroph a ges. J Infect Dis 2005;192:149-55.
- 8. Sh emon AN, S luyter R, Fernan do SL, Clarke AL, Dao-Un g LP, Skarratt KK, et al. A Thr357 to Ser polymorphism in h omozygous an d compoun d h eterozygous subjects causes absent or re duced P2 X7 function and impairs ATP-induced 7 mycobacteria l killin g by macroph a ges. J Biol Ch em 2006;281:2079-86.
- 9. American Th oracic Society. Dia gnostic stan dards an d c las- sification of tuberculosis in adults and children. Am J Res p Crit Care 2000;161:1376-95.
- 10. Nino-Moreno P, Portales-Perez D , Hernan dez-Castro B , Portales-Cervantes L , Flores-Meraz V, Baran da L , et al. P2 X7 and NRAMP1/SLC11 A1 gene polymorphism in Mexican metsizi patients with pulmonary tuberculosis. Clin Exp Immunol 2007;148:469-77.
- 11. Solini A, Ch iozzi P, More lli A, Fe llin R, Di Vir gilio F. Human primary fibroblasts in vitro Express a purinergic P2X7 rece p- tor couple d to ion fluxes, microvesic le formation an d IL-6 re lease. J Cell Sci 1999;112:297-305.
- 12. Marquet S, Sc h urr E. Genetics of susce ptibility to infectious diseases: tuberculosis an d leprosy as examples. Drug Metab Dis pos 2001;29:479-83 .
- 13. Casanova JL, Abel L. Genetic dissection of immunity to mycobacteria: th e h uman model. Annu Rev Immunol 2002 ;20:581 -620.
- 14. Gu BJ, Zh an g W, Worth in gton RA, S luyter R, DAo-Un g P, Petrou S, et al. A Glu-496 to Ala polymor phism leads to loss of function of th e human P2X7 rece ptor. J Biol Ch em 2001;276:111 35-42 .
- 15. Saunders BM, Fernan do SL, Sluyter R, Britton WJ, Wiley JS. A loss of function polymor phism in th e h uman P2X7 recep-7 tor a bolish es ATP me diated killin g of mycobacteria. J Immunol 2003 ;171:5442-6.
- 16. Sluyter R, Dalitz JG, Wiley JS. P2X7 receptor polymorphism 7 im pairs extrace llular adenosine 5-triph os ph ate in duce d interleukin-18 release from h uman monocytes. Genes Immun 2004;5:588-91 .
- 17. Fernan do SL, Saun ders BM, Sluyter R, Skarratt KK, Goldber g H , Marks GB, et a l. A polymor ph ism in th e P2X7 gene7 increases susce ptibility to extra pulmonary tuberculosis. Am J Res p Crit Care 2007;175:360-6.
- 18. Lees MP, Fuller SJ, McLeod R , Boulter NR , Miller CM, Zakrzewski AM, et a l. P2X7 receptor-mediate d killin g of an intracellular parasite, Toxo plasma gon dii, by h uman and murine macroph a ges. J Immunol 2010;184:7040-6.
- 19. Xiao J, Sun L , Jiao W, Li Z , Zhao S , Li H, et al. Lack of asso- ciation between polymor ph isms in th e P2X7 gene and 7 tuberculosis in a Ch inese Han population. FEMS Immunol Med Mic 2009;55:107-11 .
- 20. Mokrousov I, Sa poz h nikova N, Narvska ya O. Mycobac- terium tuberculosis coexistence with h umans: makin g an imprint on th e macroph age P2 X7 receptor gene? J Med Microbiol 2008;57:581-4.
- 21. Ben-Se lma W, Ben-Kahla I, Boukadida J, Harizi H. Contribution of th e P2X7 1513A/C loss of function poly-7 mor ph ism to extra pulmonary tuberculosis susce ptibility in Tunisian populations. FEMS Immunol Med Mic: 2011:1-8. DOI:10.1111/ j.1574-695X.2011.00824.x.
- 22. Möller M, Hoal EG. Current findin gs, ch allen ges an d nove l approach es in h uman genetic susceptibility to tuberculosis. Tuberculosis 2010;90:71-83 .
- 23. Li CM, Cam pbell SJ, Kumararatne DS, Bellamy R, Ruwen de C , McAdam KP, et al. Association of a polymor ph ism in th e P2X7 gene with tuberculosis in a Gambian population. J 7 In fect Dis 2002 ;186:1458-62 .