The association between single-nucleotide polymorphisms within type 1 interferon pathway genes and human immunodeficiency virus type 1 viral load in antiretroviral-naïve participants.

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  • Additional Information
    • Corporate Authors:
      INSIGHT FIRST and START study groups
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101237921 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-6405 (Electronic) Linking ISSN: 17426405 NLM ISO Abbreviation: AIDS Res Ther Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BioMed Central, 2004-
    • Subject Terms:
      HIV Infections*/virology ; HIV Infections*/genetics ; HIV Infections*/immunology ; HIV-1*/genetics ; Polymorphism, Single Nucleotide* ; Viral Load* ; Interferon Type I*/genetics; Humans ; Male ; Female ; Adult ; Genotype ; Middle Aged ; Receptor, Interferon alpha-beta/genetics ; Cohort Studies ; Disease Progression ; CD4 Lymphocyte Count
    • Abstract:
      Background: Human genetic contribution to HIV progression remains inadequately explained. The type 1 interferon (IFN) pathway is important for host control of HIV and variation in type 1 IFN genes may contribute to disease progression. This study assessed the impact of variations at the gene and pathway level of type 1 IFN on HIV-1 viral load (VL).
      Methods: Two cohorts of antiretroviral (ART) naïve participants living with HIV (PLWH) with either early (START) or advanced infection (FIRST) were analysed separately. Type 1 IFN genes (n = 17) and receptor subunits (IFNAR1, IFNAR2) were examined for both cumulated type 1 IFN pathway analysis and individual gene analysis. SKAT-O was applied to detect associations between the genotype and HIV-1 study entry viral load (log10 transformed) as a proxy for set point VL; P-values were corrected using Bonferroni (P < 0.0025).
      Results: The analyses among those with early infection included 2429 individuals from five continents. The median study entry HIV VL was 14,623 (IQR 3460-45100) copies/mL. Across 673 SNPs within 19 type 1 IFN genes, no significant association with study entry VL was detected. Conversely, examining individual genes in START showed a borderline significant association between IFNW1, and study entry VL (P = 0.0025). This significance remained after separate adjustments for age, CD4 + T-cell count, CD4 + /CD8 + T-cell ratio and recent infection. When controlling for population structure using linear mixed effects models (LME), in addition to principal components used in the main model, this was no longer significant (p = 0.0244). In subgroup analyses stratified by geographical region, the association between IFNW1 and study entry VL was only observed among African participants, although, the association was not significant when controlling for population structure using LME. Of the 17 SNPs within the IFNW1 region, only rs79876898 (A > G) was associated with study entry VL (p = 0.0020, beta = 0.32; G associated with higher study entry VL than A) in single SNP association analyses. The findings were not reproduced in FIRST participants.
      Conclusion: Across 19 type 1 IFN genes, only IFNW1 was associated with HIV-1 study entry VL in a cohort of ART-naïve individuals in early stages of their infection, however, this was no longer significant in sensitivity analyses that controlled for population structures using LME.
      (© 2024. The Author(s).)
    • References:
      Nucleic Acids Res. 2001 Jan 1;29(1):308-11. (PMID: 11125122)
      Nat Genet. 2012 Jul 22;44(8):955-9. (PMID: 22820512)
      Int Immunopharmacol. 2017 Nov;52:253-260. (PMID: 28957693)
      J Interferon Cytokine Res. 1996 Nov;16(11):919-27. (PMID: 8938567)
      Nat Rev Microbiol. 2015 Jul;13(7):403-13. (PMID: 25915633)
      Hum Genet. 2020 Jun;139(6-7):865-875. (PMID: 32409920)
      Nucleic Acids Res. 2020 Jan 8;48(D1):D498-D503. (PMID: 31691815)
      Nat Rev Genet. 2010 Dec;11(12):843-54. (PMID: 21085203)
      PLoS One. 2014 Oct 28;9(10):e111061. (PMID: 25350395)
      Database (Oxford). 2018 Jan 1;2018:. (PMID: 30576484)
      Science. 2014 Mar 21;343(6177):1243727. (PMID: 24653038)
      J Infect Dis. 2019 Sep 13;220(8):1325-1334. (PMID: 31219150)
      Lancet. 2006 Dec 16;368(9553):2125-35. (PMID: 17174704)
      Front Immunol. 2018 Jan 15;8:1823. (PMID: 29379496)
      J Infect Dis. 2017 Nov 27;216(9):1063-1069. (PMID: 28968755)
      AIDS. 2023 Mar 1;37(3):379-387. (PMID: 36473831)
      N Engl J Med. 2015 Aug 27;373(9):795-807. (PMID: 26192873)
      Bioinformatics. 2016 Sep 1;32(17):i611-i619. (PMID: 27587681)
      Elife. 2018 Dec 06;7:. (PMID: 30520725)
      Front Genet. 2019 Jan 23;9:720. (PMID: 30728828)
      Science. 2020 Oct 23;370(6515):. (PMID: 32972995)
      Gigascience. 2015 Feb 25;4:7. (PMID: 25722852)
      J Acquir Immune Defic Syndr. 2002 Sep 1;31(1):11-9. (PMID: 12352145)
      Nucleic Acids Res. 2022 Jan 7;50(D1):D687-D692. (PMID: 34788843)
      Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14658-63. (PMID: 26553974)
      Science. 2010 Dec 10;330(6010):1551-7. (PMID: 21051598)
      Nature. 2021 Mar;591(7848):92-98. (PMID: 33307546)
      Nat Immunol. 2015 Jun;16(6):577-83. (PMID: 25988890)
      Biostatistics. 2012 Sep;13(4):762-75. (PMID: 22699862)
      AIDS Behav. 2018 Jul;22(7):2277-2283. (PMID: 29427230)
      J Int AIDS Soc. 2016 Sep 19;19(1):20944. (PMID: 27649908)
      PLoS One. 2012;7(11):e50692. (PMID: 23209811)
      BMC Genomics. 2009 Jan 14;10:22. (PMID: 19144180)
      AIDS. 2004 Aug 20;18(12):1697-705. (PMID: 15280781)
      Nat Genet. 2021 Jul;53(7):1097-1103. (PMID: 34017140)
      Nature. 2023 Aug;620(7976):1025-1030. (PMID: 37532928)
      Biomed Pharmacother. 2006 Nov;60(9):569-77. (PMID: 17027223)
      Nature. 2015 Oct 1;526(7571):68-74. (PMID: 26432245)
      J Urban Health. 2006 Jan;83(1):5-17. (PMID: 16736351)
      Nucleic Acids Res. 2007 Jan;35(Database issue):D26-31. (PMID: 17148475)
      Biochim Biophys Acta Gen Subj. 2017 Feb;1861(2):335-353. (PMID: 27888147)
      Nat Genet. 2006 Aug;38(8):904-9. (PMID: 16862161)
      J Infect Dis. 2021 Dec 15;224(12):2053-2063. (PMID: 33974707)
      Cells. 2020 Jan 20;9(1):. (PMID: 31968566)
      Am J Hum Genet. 2011 Jul 15;89(1):82-93. (PMID: 21737059)
      Genome Res. 2009 Sep;19(9):1655-64. (PMID: 19648217)
      Nucleic Acids Res. 2022 Jan 7;50(D1):D988-D995. (PMID: 34791404)
      Cytokine Growth Factor Rev. 2017 Oct;37:1-16. (PMID: 28455216)
      J Infect Dis. 2022 Sep 21;226(6):1057-1068. (PMID: 35299248)
      Nat Methods. 2013 Jan;10(1):5-6. (PMID: 23269371)
      Invest New Drugs. 2020 Feb;38(1):160-171. (PMID: 31402427)
      Am J Hum Genet. 2013 Jun 6;92(6):841-53. (PMID: 23684009)
      Cells. 2019 Aug 17;8(8):. (PMID: 31426525)
      Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067. (PMID: 29165669)
      PLoS Genet. 2009 Dec;5(12):e1000791. (PMID: 20041166)
      PLoS One. 2014 Jul 30;9(7):e103593. (PMID: 25075970)
      Crit Care. 2019 Sep 5;23(1):303. (PMID: 31488196)
    • Grant Information:
      DNRF126 The Danish National Research Foundation; UM1 AI068641 United States AI NIAID NIH HHS; UM1 AI120197 United States AI NIAID NIH HHS; U01 AI136780 United States AI NIAID NIH HHS; U01 AI042170 United States AI NIAID NIH HHS; U01 AI046362 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: SKAT-O; HIV-1; Host genetics; Pathway analysis; Type 1 interferon; Viral load
    • Accession Number:
      0 (Interferon Type I)
      156986-95-7 (Receptor, Interferon alpha-beta)
      0 (IFNAR1 protein, human)
      0 (IFNAR2 protein, human)
    • Publication Date:
      Date Created: 20240502 Date Completed: 20240503 Latest Revision: 20240709
    • Publication Date:
      20240710
    • Accession Number:
      PMC11067292
    • Accession Number:
      10.1186/s12981-024-00610-x
    • Accession Number:
      38698440