Skip to main content

Advertisement

SpringerLink
Log in

Polymorphisms of IL-6 174 G/C, IL-10 -592 C/A and risk of HIV/AIDS among North Indian population

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

A growing body of evidence suggests that host genetic factors play an important role both in susceptibility to HIV infection and progression to AIDS. The present study aimed at evaluating the role of IL-6 and IL-10 gene polymorphisms on the risk of HIV susceptibility and disease progression among North Indian patients. The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques were applied to genotype IL-6 and IL-10. 300 seropositive and an equal number of age- and sex-matched seronegative control subjects were recruited for this study. There was statistically no significant variation in the frequencies of IL-6 and IL-10 genotypes among cases and controls. However, statistically non-significant association for risk of rapid disease progression was observed due to the combined effect of the IL-6 homozygous CC genotype and CC of IL-10, OR = 1.62, 95% CI = 0.38–6.91. Therefore, combined effects of the CC of IL-6 and CC of IL-10 might reduce the hosts ability to hinder viral replication after infection.

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. AIDS epidemic update (2008). http://www.unaids.org. Accessed on 12 Jan 2009

  2. Godbole S, Mehendale S (2005) HIV/AIDS epidemic in India: risk factors. Risk behaviour & strategies for prevention & control. Indian J Med Res 121:356–368

    PubMed  Google Scholar 

  3. Michael NL (2002) Host genetics and HIV—removing the mask. Nat Med 8:783–785

    Article  CAS  PubMed  Google Scholar 

  4. Ward JW, Bush TJ, Perkins HA, Lieb LE, Allen JR, Goldfinger D, Samson SM, Pepkowitz SH, Fernando LP, Holland PV, Kleinman SH, Grindon AJ, Graner PA, Rutherford GW, Holmberg SD (1989) The natural history of transfusion-associated infection with human immunodeficiency virus. Factors influencing the rate of progression to disease. N Engl J Med 321:947–952

    CAS  PubMed  Google Scholar 

  5. Fowke KR, Nagelkerke ND, Kimani J, Simonsen JN, Anzala AO, Bwayo JJ, McDonald KS, Ngugi EN, Plummer FA (1996) Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Plummer. Lancet 348:1347–1351

    Article  CAS  PubMed  Google Scholar 

  6. Rowland-Jones SL, McMichael A (1995) Immune responses in HIV-exposed seronegatives: have they repelled the virus? Curr Opin Immunol 7:448–455

    Article  CAS  PubMed  Google Scholar 

  7. Shearer GM, Clerici M (1996) Protective immunity against HIV infection: has nature done the experiment for us? Immunol Today 17:21–24

    Article  CAS  PubMed  Google Scholar 

  8. Heeney J, Beverley P, McMichael A, Shearer G, Strominger J, Wahren B, Weber J, Gotch F (1999) Immune correlates of protection from HIV and AIDS—more answers but yet more questions. Immunol Today 20:247–251

    Article  CAS  PubMed  Google Scholar 

  9. Kulkarni PS, Butera ST, Duerr AC (2003) Resistance to HIV-1 infection: lessons learned from studies of highly exposed persistently seronegative (HEPS) individuals. AIDS Rev 5:87–103

    PubMed  Google Scholar 

  10. Nowak MA, Anderson RM, McLeann AR, Wolfs TF, Goudsmit J, May RM (1991) Antigenic diversity thresholds and the development of AIDS. Science 254:963–969

    Article  CAS  PubMed  Google Scholar 

  11. Biggar RJ (1990) AIDS incubation in 1981 HIV seroconverters from different exposure groups. AIDS 4:1059–1065

    Article  CAS  PubMed  Google Scholar 

  12. Kishimoto T, Akira S, Taga T (1992) Interleukin-6 and its receptor: a paradigm for cytokines. Science 258:593–597

    Article  CAS  PubMed  Google Scholar 

  13. Pasic J, Levy WC, Sullivan MD (2003) Cytokines in depression and heart failure. Psychosom Med 65:181–193

    Article  PubMed  Google Scholar 

  14. Ramadori G, Christ B (1999) Cytokines and the hepatic acute-phase response. Semin Liver Dis 19:141–155

    Article  CAS  PubMed  Google Scholar 

  15. Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376

    Article  CAS  PubMed  Google Scholar 

  16. McNicholl JM, Smith DK, Qari SH, Hodge T (1997) Host genes and HIV: the role of the chemokine receptor gene CCR5 and its allele. Emerg Infect Dis 3:3261–3271

    Article  Google Scholar 

  17. O’Brien SJ, Dean M (1997) In search of AIDS-resistance genes. Sci Am 277:44–51

    Article  PubMed  Google Scholar 

  18. Mocellin S, Marincola FM, Young HA (2005) Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 78:1043–1105

    Article  CAS  PubMed  Google Scholar 

  19. Del Prete G, De Carli M, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S (1993) Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 150:353–360

    PubMed  Google Scholar 

  20. Westendorp RG, Langermans JA, Huizinga TW, Verweij CL, Sturk A (1997) Genetic influence on cytokine production in meningococcal disease. Lancet 349:1912–1913

    Article  CAS  PubMed  Google Scholar 

  21. Eskdale J, Keijsers V, Huizinga T, Gallagher G (1999) Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus. Genes Immun 1:151–155

    Article  CAS  PubMed  Google Scholar 

  22. Langsenlehner U, Krippl P, Renner W, Yazdani-Biuki B, Eder T, Köppel H, Wascher TC, Paulweber B, Samonigg H (2005) Interleukin-10 promoter polymorphism is associated with decreased breast cancer risk. Breast Cancer Res Treat 90:113–115

    Article  CAS  PubMed  Google Scholar 

  23. De Michele A, Martin AM, Mick R, Gor P, Wray L, Klein-Cabral M, Athanasiadis G, Colligan T, Stadtmauer E, Weber B (2003) Interleukin-6–174G→C polymorphism is associated with improved outcome in high-risk breast cancer. Cancer Res 63:8051–8056

    Google Scholar 

  24. Humphries SE, Luong LA, Ogg MS, Hawe E, Miller GJ (2001) The interleukin-6-174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 22:2243–2252

    Article  CAS  PubMed  Google Scholar 

  25. Cavet J, Dickinson AM, Norden J, Taylor PR, Jackson GH, Middleton PG (2001) Interferon-γ and interleukin-6 gene polymorphisms associate with graft-versus host disease in HLA-matched sibling bone marrow transplantation. Blood 98:1594–1600

    Article  CAS  PubMed  Google Scholar 

  26. Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M (2001) Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjogren’s syndrome and correlate with the clinical manifestations of the disease. Rheumatology 40:656–661

    Article  CAS  PubMed  Google Scholar 

  27. Pecoits-Filho R, Lindholm B, Axelsson J, Stenvinkel P (2003) Update on interleukin-6 and its role in chronic renal failure. Nephrol Dial Transplant 18:1042–1045

    Article  CAS  PubMed  Google Scholar 

  28. Bologa RM, Levine DM, Parker TS, Cheigh JS, Serur D, Stenzel KH, Rubin AL (1998) Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. Am J Kidney Dis 32:107–114

    Article  CAS  PubMed  Google Scholar 

  29. Cox ED, Hoffmann SC, DiMercurio BS, Wesley RA, Harlan DM, Kirk AD, Blair PJ (2001) Cytokine polymorphic analyses indicate ethnic differences in the allelic distribution of interleukin-2 and interleukin-6. Transplantation 72:720–772

    Article  CAS  PubMed  Google Scholar 

  30. Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 275:18138–18144

    Article  CAS  PubMed  Google Scholar 

  31. Vickers MA, Green FR, Terry C, Mayosi BM, Julier C, Lathrop M, Ratcliffe PJ, Watkins HC, Keavney B (2002) Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 53:1029–1034

    Article  CAS  PubMed  Google Scholar 

  32. Matsuda M, Salazar F, Petersson M, Masucci G, Hansson J, Pisa P, Zhang QJ, Masucci MG, Kiessling R (1994) Interleukin 10 pretreatment protects target cells from tumor- and allospecific cytotoxic T cells and downregulates HLA class I expression. J Exp Med 120:2371–2376

    Article  Google Scholar 

  33. Fortis C, Foppoli M, Gianotti L, Galli L, Citterio G, Consogno G, Gentilini O, Bragaet M (1996) Increased interleukin-10 serum levels in patients with solid tumours. Cancer Lett 104:1–5

    Article  CAS  PubMed  Google Scholar 

  34. Zhang X, Hei P, Deng L, Lin J (2007) Interleukin-10 gene promoter polymorphisms and their protein production in peritoneal fluid in patients with endometriosis. Mole Hum Reprod 13:135–140

    Article  CAS  Google Scholar 

  35. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV (1998) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1–8

    Google Scholar 

  36. van der Poll T, Marchant A, Koeogh CV, Goldman M, Lowry SF (1996) Interleukin-10 impairs host defense in murine pneumococcal pneumonia. J Infect Dis 174:994–1000

    PubMed  Google Scholar 

  37. Greenberger MJ, Strieter RM, Kunkel SL, Danforth JM, Goodman RE, Standiford TJ (1995) Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia. J Immunol 155:722–729

    CAS  PubMed  Google Scholar 

  38. Ku¨hn R, Lohler J, Rennick D, Rajewsky K, Muller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263–274

    Article  Google Scholar 

  39. Opal SM, De Pa VA (2000) Anti-inflammatory cytokines. Chest 117:1162–1172

    Article  CAS  PubMed  Google Scholar 

  40. Baier RJ, Loggins J, Yanamandra K (2006) IL-10, IL-6 and CD14 polymorphisms and sepsis outcome in ventilated very low birth weight infants. BMC Med 4:1–11

    Article  CAS  Google Scholar 

  41. De Waal Malefyt R, Abrams J, Bennett B, Figdor CG, De Vries JE (1991) Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209–1220

    Article  PubMed  Google Scholar 

  42. Murray PJ, Wang L, Onufryk C, Tepper RI, Young RA (1997) T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection. J Immunol 158:15–21

    Google Scholar 

  43. Llorente L, Richaud-Patin Y, Fior R, Alcocer-Varela J, Wijdenes J, Fourrier BM, Galanaud P, Emilie D (1994) In vivo production of interleukin-10 by non-T cells in rheumatoid arthritis, Sjogren’s syndrome, and systemic lupus erythematosus. A potential mechanism of B lymphocyte hyperactivity and autoimmunity. Arthr Rheum 37:1647–1655

    Article  CAS  Google Scholar 

  44. Mason D, Powrie F (1998) Control of immune pathology by regulatory T cells. Curr Opin Immunol 10:649–655

    Article  CAS  PubMed  Google Scholar 

  45. Kim J, Modlin RL, Moy RL, Dubinett SM, McHugh T, Nickoloff BJ, Uyemura K (1995) IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T cell immune response. J Immunol 155:2240

    CAS  PubMed  Google Scholar 

  46. Miller LC, Lynch EA, Isa S, Logan JW, Dinarello CA, Steere AC (1993) Balance of synovial fluid IL-1 beta and IL-1 receptor antagonist and recovery from lyme arthritis. Lancet 341:146–148

    Article  CAS  PubMed  Google Scholar 

  47. Girardin E, Roux-Lombard P, Grau GE, Suter P, Gallati H (1992) Imbalance between tumor necrosis factor alpha and soluble TNF receptor levels in severe meningococcemia. Immunology 76:20–23

    CAS  PubMed  Google Scholar 

  48. Villard J, Roux-Lombard P, Hugli A, Dayer JM (1993) Could natural inhibitors of tumor necrosis factor alpha modify the clinical course of fulminant meningococcemia? Critical Care Med 21:1396–1400

    Article  CAS  Google Scholar 

  49. Spear GT, MEAF A, Cohen MH, Bremer J, Landay AL (2005) Relationship of HIV RNA and cytokines in saliva from HIV-infected individuals. FEMS Immunol Med Microbiol 45:129–136

    Article  CAS  PubMed  Google Scholar 

  50. Scriba TJ, Zhang HT, Brown HL, Oxenius A, Tamm N, Fidler S, Fox J, Weber JN, Klenerman P, Day CL, Lucas M, Phillips RE (2005) HIV-1—specific CD4+ T lymphocyte turnover and activation increase upon viral rebound. J Clin Invest 115:443–450

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The authors of this paper are thankful to Dr. Ajay Wanchu’s clinical staff for the kind help and assistance they have provided during sample collection and data recording.

Author information

Authors and Affiliations

  1. Department of Biotechnology, Panjab University, Chandigarh, 160014, India

    Ranbir Chander Sobti, Nega Berhane, Salih Abdul Mahedi, Rupinder Kler & Seyed Ali Hosseini

  2. Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Vijish Kuttiat & Ajay Wanchu

Authors
  1. Ranbir Chander Sobti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nega Berhane
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Salih Abdul Mahedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rupinder Kler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seyed Ali Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vijish Kuttiat
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ajay Wanchu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ranbir Chander Sobti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sobti, R.C., Berhane, N., Mahedi, S.A. et al. Polymorphisms of IL-6 174 G/C, IL-10 -592 C/A and risk of HIV/AIDS among North Indian population. Mol Cell Biochem 337, 145–152 (2010). https://doi.org/10.1007/s11010-009-0293-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0293-0

Keywords

Search

Navigation