DOI: https://doi.org/10.14710/jbtr.v2i1.580

Polymorphisms of TLR4 Asp299Gly and TNF-α -308G/A in Leptospirosis

1dr. Kariadi Semarang Hospital, Indonesia

2Faculty of Medicine Diponegoro University, Indonesia

Received: 1 Jul 2016; Published: 30 Jul 2016.
Open Access Copyright (c) 2016 Journal of Biomedicine and Translational Research

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Abstract

Background : TLR4 Asp299Gly and TNF-α -308G/A polymorphisms have been shown to be associated with increased susceptibility and severity of infection. TLR4 Asp299Gly polymorphism could affect the host’s ability to respond to leptospira sp. TNF-α -308G/A polymorphism, is associated with the high producer of TNF-α.

Methods : Total of 36 leptospirosis patients (IgM anti leptospira and MAT positive) and healthy individual with the equal number were included. The polymorphisms were determined  by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using site spesific restriction enzyme.

Results : Distribution of  homozygous wild-type TLR4 Asp299Gly polymorphism was higher in both of groups ( 94.5:97.2%.) and homozygous mutant allele was absent. There was not significantly difference of  TLR4 Asp299Gly in leptospirosis patients and healthy group ( ρ=1.00; OR 0.5; 95%CI, 0.04-5.6) and between mild and severe leptospirosis (ρ=0.54; OR 1.54 ; 95% CI, 1.20-1.98). The presence of homozygous wild-type TNF-α -308G/A polymorphism was higher between leptospirosis patients and healthy group (100:94.5%) andhomozygous mutant allele was not found in both of the groups. No significantly different of TNF-α -308G>A polymorphism between leptospirosis patient and healthy group (ρ=0.49).

Conclusions : In this study, the polymorphisms of TLR4 Asp299Gly and TNF-α -308G/A were not associated with the susceptibility and severity of leptospirosis.

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Keywords: Leptospirosis; TLR4 Asp299 Gly polymorphis; TNF-α -308G/A polymorphism

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Section: Original Research Articles
Language : EN
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  5. Speelman P. Leptospirosis. Fauci AS (ed). Harrison's Principle of Internal
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  7. Elves A.P. Maciel DAA, Eliana A.G, et al. High Serum Nitric Oxide Levels in
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  9. Abbas AK, Pober JS, Conlin A. Innate Immunity. Cellular and Molecular Immunology. 5 ed. WB Saunders Company. Philadelphia. 2007 (5) : 22-6
  10. Maat S. Toll-Like Receptor. Airlangga University Press. Surabaya. 2009 (1) : 1-23
  11. Akira Y, Takeda K. Role of Adapters in Toll-Like Receptor Signalling. Biochem Soc Trans. 2003; 31(3): 637-42
  13. Ferwerda B, Verheijen K, Kullberg BJ, et al. Functional Consequences of Toll-like Receptor 4 Polymorphisms. Mol Mer. 2008; 14(5-6): 346-52
  14. Lorenz E, Frees KL, Schwartz DA. Relevance of Mutations in the TLR4 Receptor in Patients With Gram-Negative Septic Shock. Arch Intern Med 2002; 162(13) : 591-601
  15. Najmi KG, Sharma SK, Mehra NK. Human Toll-like receptor 4 polymorphisms TLR4 Asp299Gly and Thr399Ile influence susceptibility and severity of pulmonary tuberculosis in the Asian Indian population. Tissue Antigens. 2010; 76(2): 102-9
  16. Zakeril S , Mehrizi A, Djadid ND. Genetic variation of TLR-4, TLR-9 and TIRAP gene in Iranian malaria patients. Malar J. 2011; 10:77
  17. Arbour NC, Schutte BC, Zabner J, et al. TLR Mutations are Associated with Endotoxin Hyporesponsiveness in Humans. Nat Genet .2000; 25: 187-91
  18. Bratawijaya KG, Rengganis I. Sitokin. Imunologi Dasar. 9 ed. Jakarta: Balai Penerbit FK UI. 2010; 217-55
  19. Waterer GW, Quasney M, Cantor RM. Septic Shock and Respiratory Failure in Community-acquired Pneumonia Have Different TNF Polymorphism Associations. J Respir Crit Care Med. 2001; 13: 163
  20. Barber RC, Riverachavez FA. TLR4 and TNF-α polymorphism are associated with an increased risk for severe sepsis following burn injury. J Med 2004; 41: 808-13
  21. Cipprino C, Caruso C, Lio D,et al. TNF a-308G/A polymorphism of TNF-alpha influences immunological parameters in old subjects affected by infectious diseases. Eur J Immunogenet. 2005; 32: 13-8
  22. Ngestiningsih D, Faradz SMH. Polimorfisme alel TNF-α pada penderita DHF di Semarang. M Med Indonesia. 2006; 41: 46-50
  23. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res.1988; 16(3) : 1215
  24. Djamiatun K, Ferwerda B, Netea MG, et al. Toll-like receptor 4 polymorphism in Dengue virus –infected Children. Am J Trop Med Hyn. 2011; 85(2): 352-4
  25. RC Read, J Pullin S, Gregory, et al. A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease. J Infect Dis; 184(5): 640-2
  28. Jessen KM , Lindboe S, Petersen AL, et al. Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis. BMC Infect Dis .2007; 7(108): 1-7
  29. Schroder NW, Schuman RR. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis. 2005; 5: 156-64
  30. Zhu L, Li X, Miao C. Lack of association between TLR4 Asp299Gly and Thr399Ile polymorphisms and sepsis susceptibility: A meta-analysis. Gene. 2012; 601(2): 213-8
  31. Shan XO, Wu Y, Ding JY, et al. Gene polymorphisms of Toll-like receptors in Chinese han children with sepsis in Wenzhou. PubMed. 2010; 48(1): 15-8
  32. Song Z, Yin J, Yao C, et al. Variants in the Toll-interacting protein gene are associated with susceptibility to sepsis in the Chinese Han population. Crit Care med. 2011; 15(1): 1-10
  33. Hang J, Zhou W, Zhang H, et al. TLR4 Asp299Gly and Thr399Ile polymorphisms are rare in the Chinese population. J Endotoxin Res. 2004; 10(4): 238-40
  34. Ferwerda B, Mc Call MB, Alonso S et al. TLR4 polymorphisms, infectious Diseases, and evolutionary Pressure during Migration of Modern Humans. Proc natl Acad Sci U S A. 2007; 104(42): 16645-50
  35. Sallakci N, Ackurin G, Koksoy S, et al. TNF-alpha G-308A polymorphism is associated with rheumatic fever and correlates with increased TNF-alpha production. J Autoimmun. 2005; 25(2): 150-4
  36. Wong HR. Genetic and genomic in pediatric septic shock. Crit Care Med. 2012; 40 :1618-26
  37. Tuglular BP, Berthoux P. Berthoux F.Polymorphism of tumor necrosis factor a gene at position -308 and TNFd microsatellite in primary IgA nephropathy. Nephrol Dial Transplant 2003; 18: 724-31
  38. Song Z, Yin J, Yao C, et al. Genetic variation in the TNF gene is associated with susceptibility to severe sepsis, but not with mortality. PLoS One.2012; 7(9): e46113
  39. Teuffel O, Beyene J, Sung L. Association between tumor necrosis factor-alpha promoter-308 A/G polymorphism and susceptibility to sepsis and sepsis mortality : a systemic review and meta-analysis. Crit Care Med. 2010; 38(1): 276-82
  40. Watanabe E, Zehnbauer B, Oda S, et al. Tumor necrosis factor −308 polymorphism (rs1800629) is associated with mortality and ventilator duration in 1057 Caucasian patients. Cytokine. 2012; 60(2): 249-56
  41. Jessen KM , Lindboe S, Petersen AL, et al. Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis. BMC Infect Dis .2007; 7(108): 1-7
  42. Mergani A, Khamis AH, Haboor AB, et al. Lack of association between - 308 tumor necrosis factor polymorphism and susceptibility to cerebral malaria among Central Sudanese children . Int J Genet Mol Bio. 2010; 2(5): 67-71
  43. Andalas M, Hakimi M, Nurdiati DS, Astuti I, Imrn I, Harapan H. Association of _308G/A TNF-a gene polymorphism and spontaneous preterm birth in Acehnese ethnic group, Indonesia: This polymorphism is not associated with preterm birth. Egypt J Med Hum Genet (2015), http://dx.doi.org/10.1016/j.ejmhg.2015.05.001
  44. Ali S, Vallard AM, Kremer D, de Visser AW, Marina CA, Widjaja S, et al. Polymorphism in proinflammatory genes and susceptibility to typhoid fever and paratyphoid fever. J Interferon Cytokine Res. 2007;27(4):271-4
  45. Lamsis F, Flannery GR, White NG, Muratore R, Kaelan C, Mitchell RJ et al. Alleles and haplotypes of tumour necrosis factors (TNF) alpha and beta genes in three etnik populations of Sulawesi Indonesia. Hum Biol 2002; 74(3): 381-96

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