title: Copy Number Variation within Human β-Defensin Gene Cluster Influences Progression to AIDS in the Multicenter AIDS Cohort Study.
abstract: DEFB4/103Aencoding β-defensin 2 and 3, respectively, inhibit CXCR4-tropic (X4) viruses in vitro. We determined whetherDEFB4/103ACopy Number Variation (CNV) influences time-to-X4 and time-to-AIDS outcomes.
  
  
  
  We utilized samples from a previously published Multicenter AIDS Cohort Study (MACS), which provides longitudinal account of viral tropism in relation to the full spectrum of rates of disease progression. Using traditional models for time-to-event analysis, we investigated association betweenDEFB4/103ACNV and the two outcomes, and interaction betweenDEFB4/103ACNV and disease progression groups, Fast and Slow.
  
  
  
  Time-to-X4 and time-to-AIDS were weakly correlated. There was a stronger relationship between these two outcomes for the fast progressors.DEFB4/103ACNV was associated with time-to-AIDS, but not time-to-X4. The association between higherDEFB4/103ACNV and time-to-AIDS was more pronounced for the slow progressors.
  
  
  
  DEFB4/103ACNV was associated with time-to-AIDS in a disease progression group-specific manner in the MACS cohort. Our findings may contribute to enhancing current understanding of how genetic predisposition influences AIDS progression.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Mehlotra
authors.forename: Jean-Eudes
authors.initials: JE
authors.lastname: Dazard
authors.forename: Bangan
authors.initials: B
authors.lastname: John
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jurevic
keywords: AIDS progression; DEFB103A; DEFB4; MACS; X4 emergence; β-Defensin
references.citation: Dis Markers. 2009;27(3):121-36
references.pmid: 19893208
references.citation: PLoS Biol. 2011 Nov;9(11):e1001208
references.pmid: 22140359
references.citation: J Infect Dis. 2012 Oct 1;206(7):1012-9
references.pmid: 22837491
references.citation: Science. 2005 Mar 4;307(5714):1434-40
references.pmid: 15637236
references.citation: Genomics. 2005 Oct;86(4):423-30
references.pmid: 16039093
references.citation: J Med Virol. 2009 Dec;81(12):2036-44
references.pmid: 19856465
references.citation: AIDS. 2003 Nov 7;17(16):F39-48
references.pmid: 14571200
references.citation: Eur Respir J. 2006 Feb;27(2):253-60
references.pmid: 16452577
references.citation: Retrovirology. 2010 Mar 22;7:23
references.pmid: 20307309
references.citation: PLoS One. 2009;4(3):e4725
references.pmid: 19266104
references.citation: Am J Hum Genet. 2003 Sep;73(3):591-600
references.pmid: 12916016
references.citation: AIDS. 2007 Aug 20;21(13):1753-61
references.pmid: 17690574
references.citation: J Immunol. 2006 Jul 15;177(2):782-6
references.pmid: 16818731
references.citation: Curr Opin HIV AIDS. 2009 Mar;4(2):96-103
references.pmid: 19339947
references.citation: J Virol. 2005 Nov;79(22):14318-29
references.pmid: 16254366
references.citation: Curr Opin HIV AIDS. 2009 Mar;4(2):125-30
references.pmid: 19339951
references.citation: Hum Mutat. 2008 Oct;29(10):1247-54
references.pmid: 18470942
references.citation: J Gen Virol. 2011 Feb;92(Pt 2):247-68
references.pmid: 21106806
references.citation: AIDS. 2009 Mar 27;23(6):679-88
references.pmid: 19279442
references.citation: J Med Virol. 2012 Mar;84(3):402-13
references.pmid: 22246825
references.citation: J Acquir Immune Defic Syndr. 2009 Mar 1;50(3):331-3
references.pmid: 19194307
references.citation: J Infect Dis. 2008 Oct 15;198(8):1104-12
references.pmid: 18783316
references.citation: J Antimicrob Chemother. 2008 Feb;61(2):405-10
references.pmid: 18063598
references.citation: Cytogenet Genome Res. 2008;123(1-4):148-55
references.pmid: 19287149
references.citation: AIDS Res Hum Retroviruses. 2012 Apr;28(4):324-32
references.pmid: 21819257
references.citation: J Antimicrob Chemother. 2011 Feb;66(2):265-72
references.pmid: 21196489
references.citation: Curr Opin HIV AIDS. 2012 Sep;7(5):463-9
references.pmid: 22832712
references.citation: Lupus. 2010 Dec;19(14):1648-53
references.pmid: 20724351
references.citation: Injury. 2012 Feb;43(2):137-42
references.pmid: 21561617
references.citation: PLoS One. 2010 Dec 30;5(12):e15778
references.pmid: 21209899
references.citation: Int J Immunogenet. 2013 Aug;40(4):261-9
references.pmid: 23194186
references.citation: J Acquir Immune Defic Syndr. 2011 May 1;57(1):46-50
references.pmid: 21346588