Interleukin gene polymorphisms and susceptibility to HIV-1 infection: a meta-analysis

  • Chrissa G. Tsiara
  • Georgios K. Nikolopoulos
  • Niki L. Dimou
  • Katerina G. Pantavou
  • Pantelis G. Bagos
  • Benedicta Mensah
  • Michael Talias
  • Georgia G. Braliou
  • Dimitra Paraskeva
  • Stefanos Bonovas
  • Angelos Hatzakis
Research Article


Some subjects are repeatedly exposed to human immunodeficiency virus (HIV), yet they remain uninfected. This suggests the existence of host-resistance mechanisms. The current study synthesizes the evidence regarding the association between interleukin (IL) gene polymorphisms and HIV susceptibility. Medline, Scopus and the Web of Science databases were systematically searched, and a meta-analysis of case–control studies was conducted. Univariate and bivariate methods were used. The literature search identified 42 eligible studies involving 15,727 subjects. Evidence was obtained on eight single-nucleotide polymorphisms (SNPs): IL1A −889 C>T (rs1800587), IL1B +3953/4 C>T (rs1143634), IL4 −589/90 C>T (rs2243250), IL6 −174 G>C (rs1800795), IL10 −592 C>A (rs1800872), IL10−1082 A>G (rs1800896), IL12B −1188 A>C (rs3212227) and IL28B C>T (rs12979860). The IL1B +3953/4 C>T variant appears to increase the risk of HIV acquisition, under the assumption of a recessive genetic model (odds ratio (OR): 4.47, 95% CI: 2.35–8.52). The AA homozygotes of the IL10 -592 C>A SNP had an increased, marginally nonsignificant, risk (OR: 1.39, 95% CI: 0.97–2.01). It reached, however, significance in subanalyses (OR: 1.49, 95% CI: 1.04–2.12). Finally, the well-studied hepatitis C virus (HCV) infection IL28B (rs12979860) CT/TT genotypes were associated with a 27% decrease in HIV infection risk, especially in populations infected with HCV (OR: 0.73, 95% CI: 0.57–0.95). Interleukin signalling is perhaps important in HIV infection and some interleukin genetic variants may affect the risk of HIV acquisition. Approaches targeting specific genes and genomewide association studies should be conducted to decipher the effect of these polymorphisms.


human immunodeficiency virus susceptibility interleukin gene polymorphism single-nucleotide polymorphisms meta-analysis 

Supplementary material

12041_2018_907_MOESM1_ESM.doc (68 kb)
Supplementary material 1 (doc 68 KB)


  1. Alfano M., Crotti A., Vicenzi E. and Poli G. 2008 New players in cytokine control of HIV infection. Curr. HIV/AIDS Rep. 5, 27–32.CrossRefGoogle Scholar
  2. An P., Goedert J. J., Donfield S., Buchbinder S., Kirk G. D., Detels R. et al. 2014 Regulatory variation in HIV-1 dependency factor ZNRD1 associates with host resistance to HIV-1 acquisition. J. Infect. Dis. 210, 1539–1548.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Ank N., West H. and Paludan D. S. R. 2006 IFN-\(\uplambda \): novel antiviral cytokines. J. Interferon. Cytokine Res. 379, 373–379.CrossRefGoogle Scholar
  4. Asensi V., Rego C., Montes A. H., Collazos J., Carton J. A., Castro M. G. 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.PubMedCrossRefGoogle Scholar
  5. Avihingsanon A., Jitmitraparp S., Tangkijvanich P., Ramautarsing R. A., Apornpong T., Jirajariyavej S. et al. 2014 Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: role of vitamin D levels. J. Gastroenterol. Hepatol. 29, 1706–1714.PubMedCrossRefGoogle Scholar
  6. Begg C. B. and Mazumdar M. 1994 Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 1088–1101.PubMedCrossRefGoogle Scholar
  7. Bellanti F., Vendemiale G., Altomare E. and Serviddio G. 2012 The impact of interferon lambda 3 gene polymorphism on natural course and treatment of hepatitis C. Clin. Dev. Immunol. Article ID 849373.Google Scholar
  8. Bibert S., Roger T., Calandra T., Bochud M., Cerny A., Semmo N. et al. 2013 IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. J. Exp. Med. 210, 1109–1116.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bigham A. W., Mackelprang R. D., Celum C., De Bruyn G., Beima-Sofie K., John-Stewart G., et al. 2014 Variants in host viral replication cycle genes are associated with heterosexual HIV-1 acquisition in Africans. J. Acquir. Immune Defic. Syndr. 66, 127–134.PubMedPubMedCentralGoogle Scholar
  10. Burlone M. E., Cerutti A., Minisini R., Smirne C., Boccato E., Ceriani E. et al. 2013 IL28B polymorphism, blood interferon-alpha concentration, and disease stage of HCV mono-infected and HCV-HIV co-infected patients. Curr. HIV/AIDS Res. 11, 50–55.Google Scholar
  11. Chang J., Naif H. M., Li S., Jozwiak R., Ho-Shon M. and Cunningham A. L. 1996 The inhibition of HIV replication in monocytes by interleukin 10 is linked to inhibition of cell differentiation. AIDS Res. Hum. Retroviruses 12, 1227–1235.Google Scholar
  12. Chatterjee A., Rathore A. and Dhole T. 2009a Association of IL-4 589 C/T promoter and IL-4RalphaI50V receptor polymorphism with susceptibility to HIV-1 infection in North Indians. J. Med. Virol. 81, 959–965.PubMedCrossRefGoogle Scholar
  13. Chatterjee A., Rathore A., Sivarama P., Yamamoto N. and Dhole T. N. 2009b Genetic association of IL-10 gene promoter polymorphism and HIV-1 infection in North Indians. J. Clin. Immunol. 29, 71–77.PubMedCrossRefGoogle Scholar
  14. Chen Y., Xu H. X., Wang L. J., Liu X. X., Mahato R. I. and Zhao Y. R. 2012 Meta-analysis: IL28B polymorphisms predict sustained viral response in HCV patients treated with pegylated interferon-\(\alpha \) and ribavirin. Aliment Pharmacol. Ther. 36, 91–103.Google Scholar
  15. Clausen L. N., Astvad K., Ladelund S., Larsen M. V., Schønning K. and Benfield T. 2012 Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals. AIDS 26, 1509–1516.PubMedCrossRefGoogle Scholar
  16. Corchado S., Márquez M., Montes de Oca M., Romero-Cores P., Fernández-Gutiérrez C. and Girón-González J. A. 2013 Influence of genetic polymorphisms of tumor necrosis factor alpha and interleukin 10 genes on the risk of liver cirrhosis in HIV-HCV coinfected patients. PLoS One 8, e66619.Google Scholar
  17. Crawley E., Kay R., Sillibourne J., Patel P., Hutchinson I. and Woo P. 1999 Polymorphic haplotypes of the interleukin-10 5’-flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum. 42, 1101–1108.PubMedCrossRefGoogle Scholar
  18. Dalmasso C., Carpentier W., Meyer L., Rouzioux C., Goujard C., Chaix M. L. et al. 2008 Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study. PLoS One 3, e3907.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Davila S., Wright V. J., Khor C. C., Sim K. S., Binder A., Breunis W. B. et al. 2010 Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease. Nat. Genet. 42, 772–776.PubMedCrossRefGoogle Scholar
  20. de la Fuente C., Hinojosa C., Gilabert I., Jiménez Sousa M. Á., González J. M., Ortiz de Lejarazu R. et al. 2013 Interleukin 28B rs12979860 (CT/TT) genotype is associated with milder hepatic damage in the natural evolution of HCV/HIV coinfection. J. Interferon Cytokine Res. 33, 43–47.Google Scholar
  21. Dean M., Carrington M., Winkler C., Huttley G. A., Smith M. W., Allikmets R. et al. 1996 Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273, 1856–1862.PubMedCrossRefGoogle Scholar
  22. De Re V., Gragnani L., Fognani E., Piluso A., Izzo F., Mangia A. et al. 2014 Impact of immunogenetic IL28B polymorphism on natural outcome of HCV infection. Biomed. Res. Int. 2014, Article ID 710642.Google Scholar
  23. DerSimonian R. and Laird N. 1986 Meta-Analysis in clinical trials. Control Clin. Trails 7, 177–188.CrossRefGoogle Scholar
  24. Di Lello F. A., Caruz A., Rallon N. I., Rivero-Juarez A., Neukam K., Barreiro P. et al. 2013 Effects of the genetic pattern defined by low-density lipoprotein receptor and IL28B genotypes on the outcome of hepatitis C virus infection. Eur. J. Clin. Microbiol. Infect. Dis. 32, 1427–1435.PubMedCrossRefGoogle Scholar
  25. Duggal P., Thio C. L., Wojcik G. L., Goedert J. J., Mangia A., Latanich R. et al. 2013 Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts. Ann. Intern. Med. 158, 235–245.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Egger M., Davey Smith G., Schneider M. and Minder C. 1997 Bias in meta-analysis detected by a simple, graphical test. BMJ 315, 629–634.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Erikstrup C., Kallestrup P., Butterworth A. E., Pedersen B. K., Ostrowski S. R., Gerstoft J. et al. 2007 Reduced mortality and CD4 cell loss among carriers of the interleukin-10 S 1082G allele in a Zimbabwean cohort of HIV-1-infected adults. AIDS 21, 2283–2291.PubMedCrossRefGoogle Scholar
  28. Fellay J. 2009 Host genome influences on HIV-1 disease. Antivir. Ther. 14, 731–738.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Fellay J., Shianna K. V., Ge D., Colombo S., Weale M., Zhang K. et al. 2007 A Whole-genome association study of major determinants for host control of HIV-1. Science 317, 944–947.Google Scholar
  30. Fellay J., Ge D., Shianna K. V., Colombo S., Ledergerber B., Cirulli E. T. et al. 2009 Common genetic variation and the control of HIV-1 in humans. PLoS Genet. 5, e1000791.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Freitas F. B., Lima S. S., Feitosa R. N. M., Azevedo V. N., Ishak M. D. O. G., Ishak R. et al. 2015 Polymorphisms in the IFN\(\gamma \), IL-10, and TGF\(\beta \) genes may be associated with HIV-1 infection. Dis. Markers 2015, 1–9.CrossRefGoogle Scholar
  32. Gonçalves L. D. S., Ferreira S. M. S., Souza C. O. and Colombo A. P. V. 2009 Influence of IL-1 gene polymorphism on the periodontal microbiota of HIV-infected Brazilian individuals. Braz. Oral Res. 23, 452–459.PubMedCrossRefGoogle Scholar
  33. Grady B. P. X., Prins M., Rebers S., Molenkamp R., Geskus R. B. and Schinkel J. 2015 BMI, male sex and IL28B genotype associated with persistently high hepatitis C virus RNA levels among chronically infected drug users up to 23 years following seroconversion. J. Viral Hepat. 22, 263–271.PubMedCrossRefGoogle Scholar
  34. Grebely J., Hellard M., Applegate T., Petoumenos K., Yeung B., Feld J. J. et al. 2012 Virological responses during treatment for recent hepatitis C virus: potential benefit for ribavirin use in HCV/HIV co-infection. AIDS 26, 1653–1661.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Grebely J., Page K., Sacks-Davis R., van der Loeff M. S., Rice T. M., Bruneau J. et al. 2014 The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection. Hepatology 59, 109–120.PubMedCrossRefGoogle Scholar
  36. Gupta A. C., Trehanpati N., Sukriti S., Hissar S., Midha V., Sood A. et al. 2014 Interleukin-28b CC genotype predicts early treatment response and CT/TT genotypes predicts non-response in patients infected with HCV genotype 3. J. Med. Virol. 86, 707–712.PubMedCrossRefGoogle Scholar
  37. Hajarizadeh B., Grebely J. and Dore G. J. 2013 Epidemiology and natural history of HCV infection. Nat. Rev. Gastroenterol. Hepatol. 10, 553–562.PubMedCrossRefGoogle Scholar
  38. Hajarizadeh B., Grady B., Page K., Kim A. Y., McGovern B. H., Cox A. L. et al. 2015 Patterns of hepatitis C virus RNA levels during acute infection: the InC3 study. PLoS One 10, e0122232.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Hancock D., Gaddis N., Levy J., Bierut L., Kral A. and Johnson E. 2016 Associations of common variants in the BST2 region with HIV-1 acquisition in African American and European American people who inject drugs. AIDS 29, 767–777.CrossRefGoogle Scholar
  40. Henrich T., McLaren P., Rao S., Lin N., Hanhauser E., Giguel F. et al. 2014 Genome-wide association study of human immunodeficiency virus (HIV)-1 coreceptor usage in treatment-naive patients from an AIDS clinical trials group study. Open Forum Infect. Dis. Article ID ofu018.Google Scholar
  41. Higgins J. P. T., Thompson S. G., Deeks J. J. and Altman D. G. 2003 Measuring inconsistency in meta-analyses. BMJ 327, 557–560.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hou W., Wang X., Ye L., Zhou L., Yang Z.-Q., Riedel E. et al. 2009 Lambda interferon inhibits human immunodeficiency virus type 1 infection of macrophages. J. Virol. 83, 3834–3842.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Ingiliz P., Krznaric I., Stellbrink H. J., Knecht G., Lutz T., Noah C. et al. 2014 Multiple hepatitis C virus (HCV) reinfections in HIV-positive men who have sex with men: no influence of HCV genotype switch or interleukin-28B genotype on spontaneous clearance. HIV Med. 15, 355–361.PubMedCrossRefGoogle Scholar
  44. Ioannidis J. P., Rosenberg P. S., Goedert J. J., Ashton L. J., Benfield T. L., Buchbinder S. P. et al. 2001 Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3’A alleles on HIV-1 disease progression: an international meta-analysis of individual-patient data. Ann. Intern. Med. 135, 782–795.PubMedCrossRefGoogle Scholar
  45. Ioannidis J. P. A. and Trikalinos T. A. 2005 Early extreme contradictory estimates may appear in published research: the Proteus phenomenon in molecular genetics research and randomized trials. J. Clin. Epidemiol. 58, 543–549.PubMedCrossRefGoogle Scholar
  46. Jabłonowska E., Kołacinska A., Kuydowicz J., Przybyłowska K. and Jabłonowski Z. 2010 Interleukin-6 and the IL-6 (–174) C/G polymorphism in breast pathologies and in HIV-infected patients. Arch. Med. Sci. 6, 860–865.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Jabłonowska E., Piekarska A., Koślińska-berkan E., Omulecka A., Szymańska B. and Wójcik K. 2012 Sustained virologic response and IL28B single-nucleotide polymorphisms in patients with chronic hepatitis C treated with pegylated interferon alfa and ribavirin. Acta Biochim. Pol. 59, 333–337.PubMedGoogle Scholar
  48. Jacquelin B., Mayau V., Targat B., Liovat A. ., Kunkel D., Petitjean G. et al. 2009 Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J. Clin. Invest. 119, 3544–3555.PubMedPubMedCentralGoogle Scholar
  49. Jallow M., Teo Y. Y., Small K. S., Rockett K. A., Deloukas P., Clark T. G. et al. 2009 Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat. Genet. 41, 657–665.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Jennes W., Vuylsteke B., Borget M.-Y., Traore-Ettiegne V., Maurice C., Nolan M. et al. 2004 HIV-specific T helper responses and frequency of exposure among HIV-exposed seronegative female sex workers in Abidjan, Cote d’Ivoire. J. Infect. Dis. 189, 602–610.PubMedCrossRefGoogle Scholar
  51. Johnson E. O., Hancock D. B., Gaddis N. C., Levy J. L., Page G., Novak S. P. et al. 2015 Novel genetic locus implicated for HIV-1 acquisition with putative regulatory links to HIV replication and infectivity: a genome-wide association study. PLoS One 10, 1–15.Google Scholar
  52. Joubert B. R., Lange E. M., Franceschini N., Mwapasa V., North K. E., Meshnick S. R. et al. 2010 A whole genome association study of mother-to-child transmission of HIV in Malawi. Genome Med. 2, 17.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Kallas E., Huik K., Pauskar M., Jõgeda E. L., Karki T., Des Jarlais D. et al. 2015 Influence of interleukin 10 polymorphisms -592 and -1082 to the HIV, HBV and HCV serostatus among intravenous drug users. Infect. Genet. Evol. 30, 175–180.PubMedCrossRefGoogle Scholar
  54. Kaur G. and Mehra N. 2009 Genetic determinants of HIV-1 infection and progression to AIDS: susceptibility to HIV infection. Tissue Antigens 73, 289–301.PubMedCrossRefGoogle Scholar
  55. Kobayashi M., Suzuki F., Akuta N., Sezaki H., Suzuki Y., Hosaka T. et al. 2012 Association of two polymorphisms of the IL28B gene with viral factors and treatment response in 1,518 patients infected with hepatitis C virus. J. Gastroenterol. 47, 596–605.PubMedCrossRefGoogle Scholar
  56. Konenkov V. and Smolnikova M. 2002 Polymorphism of promotor sites of interleukins-4 and 10 and tumor necrosis factor-alpha genes in HIV-infected patients. Bull. Exp. Biol. Med. 133, 389–391.PubMedCrossRefGoogle Scholar
  57. Kwa D., van Rij R. P., Boeser-Nunnink B., Vingerhoed J. and Schuitemaker H. 2003 Association between an interleukin-4 promoter polymorphism and the acquisition of CXCR4 using HIV-1 variants. AIDS 17, 981–985.PubMedCrossRefGoogle Scholar
  58. Lane J., McLaren P. J., Dorrell L., Shianna K. V., Stemke A., Pelak K. et al. 2013 A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A. Hum. Mol. Genet. 22, 1903–1910.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Lange C. M. and Zeuzem S. 2011 IL28B single nucleotide polymorphisms in the treatment of hepatitis C. J. Hepatol. 55, 692–701.PubMedCrossRefGoogle Scholar
  60. Langhans B., Kupfer B., Braunschweiger I., Arndt S., Schulte W., Nischalke H. D. et al. 2011 Interferon-lambda serum levels in hepatitis C. J. Hepatol. 54, 859–865.PubMedCrossRefGoogle Scholar
  61. Lau J., Antman E. M., Jimenez-Silva J., Kupelnick B., Mosteller F. and Chalmers T. C. 1992 Cumulative meta-analysis of therapeutic trials for myocardial infarction. N. Engl. J. Med. 327, 248–254.PubMedCrossRefGoogle Scholar
  62. Le Clerc S., Limou S., Coulonges C., Carpentier W., Dina C., Taing L. et al. 2009 Genomewide association study of a rapid progression cohort identifies new susceptibility alleles for AIDS (ANRS Genomewide Association Study 03). J. Infect. Dis. 200, 1194–1201.PubMedCrossRefGoogle Scholar
  63. Levy J. 2009 HIV pathogenesis: 25 years of progress and persistent challenges. AIDS 23, 147–160.PubMedCrossRefGoogle Scholar
  64. Li M., Liu X., Zhou Y. and Su S. B. 2009 Interferon-\(\lambda \)s: the modulators of antivirus, antitumor, and immune responses. J. Leukoc. Biol. 86, 23–32.PubMedCrossRefGoogle Scholar
  65. Limou S., Delaneau O., Van Manen D., An P., Sezgin E., Le Clerc S. et al. 2012 Multicohort genomewide association study reveals a new signal of protection against HIV-1 acquisition. J. Infect. Dis. 205, 1155–1162.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Lingappa J. R., Petrovski S., Kahle E., Fellay J., Shianna K., McElrath M. J. et al. 2011 Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure. PLoS One 6, 6–13.Google Scholar
  67. Liu M. Q., Zhou D. J., Wang X., Zhou W., Ye L., Li J. L. et al. 2012 IFN-\(\lambda \)3 inhibits HIV infection of macrophages through the JAK-STAT pathway. PLoS One 7, e35902.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Luo M., Sainsbury J., Tuff J., Lacap P. A., Yuan X.-Y., Hirbod T. et al. 2012 A genetic polymorphism of FREM1 is associated with resistance against HIV infection in the Pumwani sex worker cohort. J. Virol. 86, 11899–11905.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Mangia A., Santoro R., Copetti M., Massari M., Piazzolla V., Spada E. et al. 2013 Treatment optimization and prediction of HCV clearance in patients with acute HCV infection. J. Hepatol. 59, 221–228.PubMedCrossRefGoogle Scholar
  70. Martin M. P., Qi Y., Goedert J. J., Hussain S. K., Kirk G. D., Hoots W. K. et al. 2010 IL28B polymorphism does not determine outcomes of hepatitis B virus or HIV infection. J. Infect. Dis. 202, 1749–1753.PubMedPubMedCentralCrossRefGoogle Scholar
  71. McLaren P. J., Coulonges C., Ripke S., van den Berg L., Buchbinder S., Carrington M. et al. 2013 Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls. PLoS Pathog. 9, e1003515.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Minelli C., Thompson J. R., Abrams K. R., Thakkinstian A. and Attia J. 2005 The choice of a genetic model in the meta-analysis of molecular association studies. Int. J. Epidemiol. 34, 1319–1328.PubMedCrossRefGoogle Scholar
  73. Miyazawa M., Lopalco L., Mazzotta F., Lo Caputo S., Veas F. and Clerici M. 2009 The ‘immunologic advantage’ of HIV-exposed seronegative individuals. AIDS 23, 161–175.PubMedCrossRefGoogle Scholar
  74. Modi W. S., O’Brien T. R., Vlahov D., Buchbinder S., Gomperts E., Phair J. et al. 2003 Haplotype diversity in the interleukin-4 gene is not associated with HIV-1 -transmission and aids progression. Immunogenetics 55, 157–164.PubMedCrossRefGoogle Scholar
  75. Moher D., Liberati A., Tetzlaff J. and Altman D. G. 2010 Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int. J. Surg. 8, 336–341.PubMedCrossRefGoogle Scholar
  76. Morrow M. P., Pankhong P., Laddy D. J., Schoenly K. A., Yan J., Cisper N. et al. 2009 Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity. Blood 113, 5868–5877.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Mosser D. M. 2008 Interleukin-10: new perspectives on an old cytokine. Immunol. Rev. 226, 205–218.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Naggie S., Osinusi A., Katsounas A., Lempicki R., Herrmann E., Thompson A. J. et al. 2012 Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: impaired viral kinetics and therapeutic response. Hepatology 56, 444–454.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Naicker D. D., Werner L., Kormuth E., Passmore J., Mlisana K., Karim S. A. et al. 2009 Interleukin-10 promoter polymorphisms influence HIV-1 susceptibility and primary HIV-1 pathogenesis. J. Infect. Dis. 200, 448–452.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Nakayama E. E., Meyer L., Iwamoto A., Persoz A., Nagai Y., Rouzioux C. et al. 2002 Protective effect of interleukin-4-589T polymorphism on human immunodeficiency virus type 1 disease progression: relationship with virus load. J. Infect. Dis. 185, 1183–1186.PubMedCrossRefGoogle Scholar
  81. Nakayama E. M. I. E., Hoshino Y., Xin X., Liu H., Goto M., Watanabe N. et al. 2000 Polymorphism in the interleukin-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium-inducing phenotype. J. Virol. 74, 5452–5459.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Nattermann J., Vogel M., Berg T., Danta M., Axel B., Mayr C. et al. 2007 Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients. Hepatology 46, 1016–1025.PubMedCrossRefGoogle Scholar
  83. Neukam K., Barreiro P., Rivero-Juárez A., Caruz A., Mira J. A., Camacho A. et al. 2013 Pegylated interferon plus ribavirin is suboptimal in IL28B CC carriers without rapid response. J. Infect. 67, 59–64.PubMedCrossRefGoogle Scholar
  84. Ouyang W., Rutz S., Crellin N. K., Valdez P. A. and Hymowitz S. G. 2011 Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu. Rev. Immunol. 29, 71–109.PubMedCrossRefGoogle Scholar
  85. Pemberton L. A., Stone E., Price P., Van Bockxmeer F. and Brew B. J. 2008 The relationship between ApoE, TNFA, IL1a, IL1b and IL12b genes and HIV-1-associated dementia. HIV Med. 9, 677–680.PubMedCrossRefGoogle Scholar
  86. Pereyra F., Jia X., McLaren P. J., Kadie C. M., Carlson J. M., Heckerman D. et al. 2011 The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330, 1551–1557.Google Scholar
  87. Petitti D. B. 2000 Meta-analysis, decision analysis, and cost-effectiveness analysis, 2nd edition. Oxford University Press, Oxford.Google Scholar
  88. Petrovski S., Fellay J., Shianna K., Carpenetti N., Kumwenda J., Kamanga G. et al. 2011 Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. AIDS 25, 513–518.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Pociot F., Mølvig J., Wogensen L., Worsaae H. and Nerup J. 1992 A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur. J. Clin. Invest. 22, 396–402.PubMedCrossRefGoogle Scholar
  90. Poli G., Kinter A. and Fauci A. 1994 Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. Proc. Natl. Acad. Sci. USA 91, 108–112.Google Scholar
  91. Pontillo A., Oshiro T. M., Girardelli M., Kamada A. J., Sergio Crovella P. and Duarte A. J. 2012 Polymorphisms in inflammasome’ genes and susceptibility to HIV-1 infection. J. Acquir. Immune Defic. Syndr. 59, 121–125.PubMedCrossRefGoogle Scholar
  92. Price P., Calder D. M., Witt C. S., Allcock R. J., Christiansen F. T., Davies G. R. et al. 1999 Periodontal attachment loss in HIV-infected patients is associated with the major histocompatibility complex 8.1 haplotype (HLA-A1,B8,DR3). Tissue Antigens 54, 391–399.PubMedCrossRefGoogle Scholar
  93. Price P., Morahan G., Huang D., Stone E., Cheong K. Y. M., Castley A. et al. 2002 Polymorphisms in cytokine genes define subpopulations of HIV-1 patients who experienced immune restoration diseases. AIDS 16, 2043–2047.PubMedCrossRefGoogle Scholar
  94. Puhan M., Van Natta M., Palella F., Addessi A. and Meinert C. 2010 Excess mortality in patients with AIDS in the era of highly active antiretroviral therapy: temporal changes and risk factors. Clin. Infect. Dis. 51, 947–956.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Rallon N. I., Restrepo C., Naggie S., Lopez M., del Romero J., Goldstein D. et al. 2011 Interleukin-28B gene polymorphisms do not influence the susceptibility to HIV-infection or CD4 cell decline. AIDS 25, 269–271.PubMedCrossRefGoogle Scholar
  96. Ramaseri Sunder S., Hanumanth S. R., Nagaraju R. T., Neela Venkata S. K., Suryadevara N. C., Pydi S. S. et al. 2012 IL-10 high producing genotype predisposes HIV infected individuals to TB infection. Hum. Immunol. 73, 605–611.Google Scholar
  97. Ramezani A., Kalantar E., Aghakhani A., Banifazl M., Foroughi M., Hosseini S. et al. 2015 Lack of association between interleukin-10 gene promoter polymorphisms with HIV susceptibility and progression to AIDS. Iran J. Pathol. 10, 141–148.PubMedPubMedCentralGoogle Scholar
  98. Sajadi M. M., Shakeri N., Talwani R., Howell C. D., Pakyz R., Redfield R. R. et al. 2011 IL28B genotype does not correlate with HIV control in African Americans. Clin. Transl. Sci. 4, 282–284.PubMedPubMedCentralCrossRefGoogle Scholar
  99. Salanti G., Higgins J. P. T., Trikalinos T. A. and Ioannidis J. P. A. 2007 Bayesian meta-analysis and meta-regression for gene-disease associations and deviations from Hardy-Weinberg equilibrium. Stat. Med. 26, 553–567.PubMedCrossRefGoogle Scholar
  100. Samson M., Libert F., Doranz B. J., Rucker J., Liesnard C., Farber C. M. et al. 1996 Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382, 722–725.PubMedCrossRefGoogle Scholar
  101. Saumoy M., López-Dupla M., Veloso S., Alonso-Villaverde C., Domingo P., Broch M. et al. 2008 The IL-6 system in HIV-1-infection and in HAART-related fat redistribution syndromes. AIDS 22, 893–896.PubMedCrossRefGoogle Scholar
  102. Schaid D. J. and Jacobsen S. J. 1999 Biased tests of association: comparisons of allele frequencies when departing from Hardy-Weinberg proportions. Am. J. Epidemiol. 149, 706–711.PubMedCrossRefGoogle Scholar
  103. Seaberg E. C., Witt M. D., Jacobson L. P., Detels R., Rinaldo C. R., Margolick J. B. et al. 2015 Spontaneous clearance of the Hepatitis C virus among men who have sex with men. Clin. Infect. Dis. 61, 1381–1388.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Serra C., Biolchini A., Mei A., Kotenko S. and Dolei A. 2008 Type III and I interferons increase HIV uptake and replication in human cells that overexpress CD4, CCR, and CXCR4. AIDS Res. Hum. Retroviruses 24, 173–180.PubMedCrossRefGoogle Scholar
  105. Sheppard P., Kindsvogel W., Xu W., Henderson K., Schlutsmeyer S., Whitmore T. E. et al. 2003 IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat. Immunol. 4, 63–68.PubMedCrossRefGoogle Scholar
  106. Shin H. D., Winkler C., Stephens J. C., Bream J., Young H., Goedert J. J. et al. 2000 Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. Proc. Natl. Acad. Sci. USA 97, 14467–14472.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Smolnikova M., Freidin M., Konenkov V. and Puzirev V. 2001 Genetic polymorphism in the interleukin-4 promoter region in human immunodeficiency virus. Eur. J. Immunogenet. 28, 243.Google Scholar
  108. Sobti R. C., Berhane N., Mahedi S. A., Kler R., Hosseini S. A., Kuttiat V. et al. 2010a 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.PubMedCrossRefGoogle Scholar
  109. Sobti R. C., Salih A. M., Nega B., Seyed A. H., Rupinder K., Vijesh K. et al. 2010b Insights into the role of IL-12B and IFN-gamma cytokine gene polymorphisms in HIV-1/AIDS infection. Folia Biol. (Praha). 56, 110–115Google Scholar
  110. Stenkvist J., Sönnerborg A. and Weiland O. 2013 HCV RNA decline in chronic HCV genotype 2 and 3 during standard of care treatment according to IL28B polymorphism. J. Viral Hepat. 20, 193–199.PubMedCrossRefGoogle Scholar
  111. Stroup D. F., Berlin J. A., Morton S. C., Olkin I., Williamson G. D., Rennie D. et al. 2000 Meta-analysis of observational studies in epidemiology: a proposal for reporting. Jama 283, 2008–2012.PubMedCrossRefGoogle Scholar
  112. Thomas D. L., Thio C. L., Martin M. P., Qi Y., Ge D., O’Huigin C. et al. 2009 Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461, 798–801.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Thye T., Vannberg F. O., Wong S. H., Owusu-Dabo E., Osei I., Gyapong J. et al. 2010 Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2. Nat. Genet. 42, 739–741.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Uccellini L., Tseng F. C., Monaco A., Shebl F. M., Pfeiffer R., Dotrang M. et al. 2012 HCV RNA levels in a multiethnic cohort of injection drug users: human genetic, viral and demographic associations. Hepatology 56, 86–94.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Urban T. J., Thompson A. J., Bradrick S. S., Fellay J., Schuppan D., Cronin K. D. et al. 2010 IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology 52, 1888–1896.PubMedPubMedCentralCrossRefGoogle Scholar
  116. van Manen D., van ‘t Wout A. B. and Schuitemaker H. 2012 Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics. Retrovirology 9, 70.Google Scholar
  117. Wang C., Song W., Lobashevsky E. and Wilson C. M. 2004 Cytokine and chemokine gene polymorphisms among ethnically diverse North Americans with HIV-1 infection. J. Acquir. Immune Defic. Syndr. 35, 446–454.PubMedCrossRefGoogle Scholar
  118. Weissman D., Poli G. and Fauci A. S. 1994 Interleukin 10 blocks HIV replication in macrophages by inhibiting the autocrine loop of tumor necrosis factor alpha and interleukin 6 induction of virus. AIDS Res. Hum. Retroviruses 10, 1199–1206.PubMedCrossRefGoogle Scholar
  119. Wichukchinda N. and Nakayama E. E. 2006 Protective effects of IL4-589T and RANTES-28G on HIV-1 disease progression in infected Thai females. AIDS 20, 189–196.PubMedCrossRefGoogle Scholar
  120. Yang M., Rao H. Y., Feng B., Zhang W. and Wei L. 2013 Impact of interleukin 28B polymorphisms on spontaneous clearance of hepatitis C virus infection: a meta-analysis. J. Gastroenterol. Hepatol. 28, 1114–1121.PubMedCrossRefGoogle Scholar
  121. Ydreborg M., Westin J., Rembeck K., Lindh M., Norrgren H., Holmberg A. et al. 2013 Impact of IL28B-related single nucleotide polymorphisms on liver transient elastography in chronic hepatitis C infection. PLoS One 8, 1–8.CrossRefGoogle Scholar
  122. Yuan H., Adams-Huet B., Petersen T., Attar N., Lee W. and Jain M. 2012 A single nucleotide polymorphism in IL28B affects viral evolution of hepatitis C quasispecies after pegylated interferon and ribavirin therapy. J. Med. Virol. 84, 1913–1919.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Zeremski M., Dimova R. B., Makeyeva J., Sipley J. D., Jacobson I. M., Rennert H. et al. 2013 IL28B polymorphism, pretreatment CXCL10, and HCV RNA levels predict treatment response in racially diverse HIV / HCV coinfected and HCV monoinfected patients. J. Acquir. Immune Defic. Syndr. 63, 9–16.PubMedCrossRefGoogle Scholar
  124. Zheng M. H., Li Y., Xiao D. D., Shi K. Q., Fan Y. C., Chen L. L. et al. 2013 Interleukin-28B rs12979860C/T and rs8099917T/G contribute to spontaneous clearance of hepatitis C virus in Caucasians. Gene 518, 479–482.PubMedCrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  • Chrissa G. Tsiara
    • 1
    • 2
  • Georgios K. Nikolopoulos
    • 3
  • Niki L. Dimou
    • 4
  • Katerina G. Pantavou
    • 3
  • Pantelis G. Bagos
    • 4
  • Benedicta Mensah
    • 5
  • Michael Talias
    • 6
  • Georgia G. Braliou
    • 4
  • Dimitra Paraskeva
    • 1
  • Stefanos Bonovas
    • 7
    • 8
  • Angelos Hatzakis
    • 2
  1. 1.Hellenic Centre for Disease Control and PreventionAthensGreece
  2. 2.Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  3. 3.Medical SchoolUniversity of CyprusStrovolosCyprus
  4. 4.Department of Computer Science and Biomedical InformaticsUniversity of ThessalyLamiaGreece
  5. 5.Noguchi Memorial Institute for Medical ResearchUniversity of GhanaAccraGhana
  6. 6.Healthcare Management Postgraduate ProgramOpen University of CyprusNicosiaCyprus
  7. 7.Humanitas Clinical and Research CenterMilanItaly
  8. 8.Department of Biomedical SciencesHumanitas UniversityMilanItaly

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