Skip to main content

Advertisement

SpringerLink
Log in

IL-1β (−511T/C) gene polymorphism not IL-1β (+3953T/C) and LT-α (+252A/G) gene variants confers susceptibility to visceral leishmaniasis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Lymphotoxin-α (LT-α) and interleukin-1beta (IL-1β) are proinflammatory cytokines playing important roles in immunity against Leishmania infection and the outcome of the disease. As cytokine productions are under the genetic control, this study tried to find any probable relationship between these cytokine gene polymorphisms and the susceptibility to visceral leishmaniasis in Iranian pediatric patients. Ninety-five pediatric patients involved with visceral leishmaniasis and 128 non-relative healthy people, from the same area as the patients, were genotyped for LT-α (+252A/G) and IL-1β (+3953T/C and −511T/C) gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). There was not found any significant differences in allele and genotype frequencies of LT-α (+252A/G) and IL-1β (+3953) among the study groups. However, the frequency of IL-1β −511TT genotype was higher in the controls (P = 0.0004) while the frequency of IL-1β −511CC genotype and C allele were higher in the patients (P = 0.008 and P = 0.00006, respectively). Furthermore, IL-1β CC (−511/+3953) haplotype was more frequent in VL patients compared with the controls (P = 0.0002) and the distribution of TT haplotype was higher in the controls compared with the patients (P = 0.003). In conclusion, based on the results, IL-1β −511C allele, CC genotype and CC (−511/+3953) haplotype could be considered as the susceptibility factors for visceral leishmaniasis while IL-1β −511TT genotype, T allele and TT haplotype (−511/+3953) might be counted as the influential factors for resistance to the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Herwaldt BL (1999) Leishmaniasis. Lancet 354:1191–1199

    Article  PubMed  CAS  Google Scholar 

  2. Desjeux P (2004) Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27:305–318

    Article  PubMed  CAS  Google Scholar 

  3. Pearson RD, Sousa AQ (1996) Clinical spectrum of Leishmaniasis. Clin Infect Dis 22:1–13

    Article  PubMed  CAS  Google Scholar 

  4. Ansari NA, Ramesh V, Salotra P (2006) Interferon (IFN)-gamma, tumor necrosis factor-alpha, interleukin-6, and IFN-gamma receptor 1 are the major immunological determinants associated with post-kala azar dermal leishmaniasis. J Infect Dis 194:958–965

    Article  PubMed  CAS  Google Scholar 

  5. Kurkjian KM, Mahmutovic AJ, Kellar KL, Haque R, Bern C, Secor WE (2006) Multiplex analysis of circulating cytokines in the sera of patients with different clinical forms of visceral leishmaniasis. Cytometry 69:353–358

    Article  PubMed  Google Scholar 

  6. Wilhelm P, Ritter U, Labbow S et al (2001) Rapidly fatal leishmaniasis in resistant C57BL/6 mice lacking TNF. J Immunol 166:4012–4019

    PubMed  CAS  Google Scholar 

  7. Voronov E, Dotan S, Gayvoronsky L et al (2010) IL-1-induced inflammation promotes development of leishmaniasis in susceptible BALB/c mice. Int Immunol 22:245–257

    Article  PubMed  CAS  Google Scholar 

  8. de Lima VM, Peiro JR, de Oliveira Vasconcelos R (2007) IL-6 and TNF-alpha production during active canine visceral leishmaniasis. Vet Immunol Immunopathol 115:189–193

    Article  PubMed  Google Scholar 

  9. Xu G, Liu D, Fan Y et al (2007) Lymphotoxin alpha beta 2 (membrane lymphotoxin) is critically important for resistance to Leishmania major infection in mice. J Immunol 179:5358–5366

    PubMed  CAS  Google Scholar 

  10. Engwerda CR, Ato M, Stager S, Alexander CE, Stanley AC, Kaye PM (2004) Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of Leishmania donovani infection. Am J Pathol 165:2123–2133

    Article  PubMed  CAS  Google Scholar 

  11. Murray HW, Jungbluth A, Ritter E, Montelibano C, Marino MW (2000) Visceral leishmaniasis in mice devoid of tumor necrosis factor and response to treatment. Infect Immunol 68:6289–6293

    Article  CAS  Google Scholar 

  12. Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501

    Article  PubMed  CAS  Google Scholar 

  13. Liew FY, Li Y, Millott S (1990) Tumor necrosis factor-alpha synergizes with IFN-gamma in mediating killing of Leishmania major through the induction of nitric oxide. J Immunol 145:4306–4310

    PubMed  CAS  Google Scholar 

  14. Liew FY, Li Y, Millott S (1990) Tumour necrosis factor (TNF-alpha) in leishmaniasis. II. TNF-alpha-induced macrophage leishmanicidal activity is mediated by nitric oxide from l-arginine. Immunology 71:556–559

    PubMed  CAS  Google Scholar 

  15. Cuff CA, Sacca R, Ruddle NH (1999) Differential induction of adhesion molecule and chemokine expression by LTalpha3 and LTalphabeta in inflammation elucidates potential mechanisms of mesenteric and peripheral lymph node development. J Immunol 162:5965–5972

    PubMed  CAS  Google Scholar 

  16. Sacca R, Cuff CA, Lesslauer W, Ruddle NH (1998) Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling. J Immunol 160:485–491

    PubMed  CAS  Google Scholar 

  17. Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147

    PubMed  CAS  Google Scholar 

  18. Auron PE (1998) The interleukin 1 receptor: ligand interactions and signal transduction. Cytokine Growth Factor Rev 9:221–237

    Article  PubMed  CAS  Google Scholar 

  19. Von Stebut E, Ehrchen JM, Belkaid Y et al (2003) Interleukin 1alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. J Exp Med 198:191–199

    Article  Google Scholar 

  20. Kostka SL, Knop J, Konur A, Udey MC, von Stebut E (2006) Distinct roles for IL-1 receptor type I signaling in early versus established Leishmania major infections. J Invest Dermatol 126:1582–1589

    Article  PubMed  CAS  Google Scholar 

  21. Rasouli M, Kiany S, Behbin M (2008) Interleukin-10 gene polymorphisms and susceptibility to brucellosis in Iranian patients. Iran J Immunol 5:131–135

    PubMed  CAS  Google Scholar 

  22. Rasouli M, Kalani M, Moravej A, Kiany S (2011) Interleukin-18 single nucleotide polymorphisms contribute to the susceptibility to brucellosis in Iranian patients. Cytokine 54:272–276

    Article  PubMed  CAS  Google Scholar 

  23. Rasouli M, Kiany S (2007) Association of interferon-gamma and interleukin-4 gene polymorphisms with susceptibility to brucellosis in Iranian patients. Cytokine 38:49–53

    Article  PubMed  CAS  Google Scholar 

  24. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV (1998) Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis. Tuber Lung Dis 79:83–89

    Article  PubMed  CAS  Google Scholar 

  25. Kamali-Sarvestani E, Rasouli M, Mortazavi H, Gharesi-Fard B (2006) Cytokine gene polymorphisms and susceptibility to cutaneous leishmaniasis in Iranian patients. Cytokine 35:159–165

    Article  PubMed  CAS  Google Scholar 

  26. Trajkov D, Trajchevska M, Arsov T et al (2009) Association of 22 cytokine gene polymorphisms with tuberculosis in Macedonians. Indian J Tuberculosis 56(3):117–131

    Google Scholar 

  27. Messer G, Spengler U, Jung MC et al (1991) Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. J Exp Med 173:209–219

    Article  PubMed  CAS  Google Scholar 

  28. Asensi V, Rego C, Montes AH et al (2008) IL-1beta (+3954C/T) polymorphism could protect human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treatment (HAART) against lipodystrophic syndrome. Genet Med 10:215–223

    Article  PubMed  CAS  Google Scholar 

  29. Chakravorty M, Ghosh A, Choudhury A, Santra A, Hembrum J, Roychoudhury S (2006) Interaction between IL1B gene promoter polymorphisms in determining susceptibility to Helicobacter pylori associated duodenal ulcer. Hum Mutat 27:411–419

    Article  PubMed  CAS  Google Scholar 

  30. Fang XM, Schroder S, Hoeft A, Stuber F (1999) Comparison of two polymorphisms of the interleukin-1 gene family: interleukin-1 receptor antagonist polymorphism contributes to susceptibility to severe sepsis. Crit Care Med 27:1330–1334

    Article  PubMed  CAS  Google Scholar 

  31. Walley AJ, Aucan C, Kwiatkowski D, Hill AV (2004) Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria in a Gambian case-control study. Eur J Hum Genet 12:132–138

    Article  PubMed  CAS  Google Scholar 

  32. McDevitt MJ, Wang HY, Knobelman C et al (2000) Interleukin-1 genetic association with periodontitis in clinical practice. J Periodontol 71:156–163

    Article  PubMed  CAS  Google Scholar 

  33. Rasouli M, Kiany S, Moravej A, Kalani M (2010) Interleukin-12 and Tumor necrosis factor-Β Gene polymorphisms as genetic susceptibility factors for Brucellosis in Iranian patients. Iran Red Crescent Med J 12:266–271

    Google Scholar 

  34. Pociot F, Mølvig J, Wogensen L, Worsaae H, Nerup J (1992) A TaqI polymorphism in the human interleukin- 1beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest 22:396–402

    Article  PubMed  CAS  Google Scholar 

  35. di Giovine FS, Takhsh E, Blakemore AI, Duff GW (1992) Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta). Hum Mol Genet 1:450

    Article  PubMed  Google Scholar 

  36. Beutler B, Grau GE (1993) Tumor necrosis factor in the pathogenesis of infectious diseases. Crit Care Med 21:S423–S435

    Article  PubMed  CAS  Google Scholar 

  37. Vassalli P (1992) The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10:411–452

    Article  PubMed  CAS  Google Scholar 

  38. Bogdan C, Moll H, Solbach W, Rollinghoff M (1990) Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes. Eur J Immunol 20:1131–1135

    Article  PubMed  CAS  Google Scholar 

  39. Pociot F, Briant L, Jongeneel CV et al (1993) Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. Eur J Immunol 23:224–231

    Article  PubMed  CAS  Google Scholar 

  40. Sharma S, Rathored J, Ghosh B, Sharma SK (2010) Genetic polymorphisms in TNF genes and tuberculosis in North Indians. BMC Infect Dis 10:165

    Article  PubMed  Google Scholar 

  41. Li C, Xia B, Yang Y, Li J, Xia HH (2005) TNF gene polymorphisms and Helicobacter Pylori infection in gastric carcinogenesis in Chinese population. Am J Gastroenterol 100:290–294

    Article  PubMed  CAS  Google Scholar 

  42. Farshad S, Rasouli M, Jamshidzadeh A et al (2010) IL-1β (+3953 C/T) and IL-8 (−251 A/T) gene polymorphisms in H. pylori mediated gastric disorders. Iran J Immunol 7:96–108

    PubMed  CAS  Google Scholar 

  43. Asensi V, Rego C, Montes AH et al (2008) IL-1beta (+3954C/T) polymorphism could protect human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treatment (HAART) against lipodystrophic syndrome. Genet Med 10(3):215–223

    Article  PubMed  CAS  Google Scholar 

  44. Chakravorty M, Ghosh A, Choudhury A, Santra A, Hembrum J, Roychoudhury S (2006) Interaction between IL1B gene promoter polymorphisms in determining susceptibility to Helicobacter pylori associated duodenal ulcer. Hum Mutat 27(5):411–419

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We would like to thank Miss. Esmat Kazemi for fundamental English editing. This study was financially supported by a Grant No. 85-3 from Prof. Alborzi Clinical Microbiology Research Center affiliated with Shiraz University of Medical Sciences.

Author information

Authors and Affiliations

  1. Department of Microbiology, Fasa University of Medical Sciences, Fasa, Fars, Iran

    Ali Moravej, Sohrab Najafipour, Amin Koohpayeh & Abbas Abdollahi

  2. Department of Immunology, Prof. Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, 71937-11351, Shiraz, Fars, Iran

    Manoochehr Rasouli, Mehdi Kalani, Sadaf Asaei & Simin Kiany

Authors
  1. Ali Moravej
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manoochehr Rasouli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehdi Kalani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sadaf Asaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simin Kiany
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sohrab Najafipour
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Amin Koohpayeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Abbas Abdollahi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manoochehr Rasouli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moravej, A., Rasouli, M., Kalani, M. et al. IL-1β (−511T/C) gene polymorphism not IL-1β (+3953T/C) and LT-α (+252A/G) gene variants confers susceptibility to visceral leishmaniasis. Mol Biol Rep 39, 6907–6914 (2012). https://doi.org/10.1007/s11033-012-1517-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1517-z

Keywords

Search

Navigation