PMID- 25734091
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150303
LR  - 20201001
IS  - 2328-8957 (Print)
IS  - 2328-8957 (Electronic)
IS  - 2328-8957 (Linking)
VI  - 1
IP  - 1
DP  - 2014 Mar
TI  - Genome-Wide Association Study of Human Immunodeficiency Virus (HIV)-1 Coreceptor 
      Usage in Treatment-Naive Patients from An AIDS Clinical Trials Group Study.
PG  - ofu018
LID - 10.1093/ofid/ofu018 [doi]
LID - ofu018
AB  - OBJECTIVES: We conducted a genome-wide association study to explore whether 
      common host genetic variants (>5% frequency) were associated with presence of 
      virus able to use CXCR4 for entry. METHODS: Phenotypic determination of human 
      immunodeficiency virus (HIV)-1 coreceptor usage was performed on pretreatment 
      plasma HIV-1 samples from treatment-naive participants in AIDS Clinical Trials 
      Group A5095, a study of initial antiretroviral regimens. Associations between 
      genome-wide single-nucleotide polymorphisms (SNPs), CCR5 Delta32 genotype, and human 
      leukocyte antigen (HLA) class I alleles and viral coreceptor usage were explored. 
      RESULTS: Viral phenotypes were obtained from 593 patients with available 
      genome-wide SNP data. Forty-four percent of subjects had virus capable of using 
      CXCR4 for entry as determined by phenotyping. Overall, no associations, including 
      those between polymorphisms in genes encoding viral coreceptors and their 
      promoter regions or in HLA genes previously associated with HIV-1 disease 
      progression, passed the statistical threshold for genome-wide significance (P < 
      5.0 x 10(-8)) in any comparison. However, the presence of viruses able to use 
      CXCR4 for entry was marginally associated with the CCR5 Delta32 genotype in the 
      nongenome-wide analysis. CONCLUSIONS: No human genetic variants were 
      significantly associated with virus able to use CXCR4 for entry at the 
      genome-wide level. Although the sample size had limited power to definitively 
      exclude genetic associations, these results suggest that host genetic factors, 
      including those that influence coreceptor expression or the immune pressures 
      leading to viral envelope diversity, are either rare or have only modest effects 
      in determining HIV-1 coreceptor usage.
FAU - Henrich, Timothy J
AU  - Henrich TJ
AD  - Division of Infectious Diseases , Brigham and Women's Hospital , Boston, 
      Massachusetts ; Harvard Medical School , Boston, Massachusetts.
FAU - McLaren, Paul J
AU  - McLaren PJ
AD  - Ecole Polytechnique Federale de Lausanne and University of Lausanne , Switzerland 
      ; University Hospital and University of Lausanne , Switzerland ; Swiss Institute 
      of Bioinformatics , Switzerland.
FAU - Rao, Suhas S P
AU  - Rao SS
AD  - Harvard University, Cambridge, Massachusetts.
FAU - Lin, Nina H
AU  - Lin NH
AD  - Massachusetts General Hospital , Boston, Massachusetts ; Harvard Medical School , 
      Boston, Massachusetts.
FAU - Hanhauser, Emily
AU  - Hanhauser E
AD  - Division of Infectious Diseases , Brigham and Women's Hospital , Boston, 
      Massachusetts.
FAU - Giguel, Francoise
AU  - Giguel F
AD  - Massachusetts General Hospital , Boston, Massachusetts.
FAU - Gulick, Roy M
AU  - Gulick RM
AD  - Weill Medical College of Cornell University, New York, New York.
FAU - Ribaudo, Heather
AU  - Ribaudo H
AD  - Harvard Medical School , Boston, Massachusetts ; Harvard School of Public Health.
FAU - de Bakker, Paul I W
AU  - de Bakker PI
AD  - Harvard Medical School , Boston, Massachusetts ; Program in Medical and 
      Population Genetics , Broad Institute of Harvard and MIT , Boston, Massachusetts 
      ; Department of Medical Genetics and Department of Epidemiology , University 
      Medical Center Utrecht , Utrecht , The Netherlands ; Divison of Genetics , 
      Brigham and Women's Hospital , Boston, Massachusetts.
FAU - Kuritzkes, Daniel R
AU  - Kuritzkes DR
AD  - Division of Infectious Diseases , Brigham and Women's Hospital , Boston, 
      Massachusetts ; Harvard Medical School , Boston, Massachusetts.
LA  - eng
GR  - KL2 RR025757/RR/NCRR NIH HHS/United States
GR  - R37 AI055357/AI/NIAID NIH HHS/United States
GR  - U01 AI068634/AI/NIAID NIH HHS/United States
GR  - U01 AI068636/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20140522
PL  - United States
TA  - Open Forum Infect Dis
JT  - Open forum infectious diseases
JID - 101637045
PMC - PMC4324186
OTO - NOTNLM
OT  - CCR5 Delta32 mutation
OT  - HIV-1
OT  - genome-wide association study
OT  - viral coreceptor usage
OT  - viral tropism
EDAT- 2015/03/04 06:00
MHDA- 2015/03/04 06:01
PMCR- 2014/05/22
CRDT- 2015/03/04 06:00
PHST- 2014/01/13 00:00 [received]
PHST- 2014/04/03 00:00 [accepted]
PHST- 2015/03/04 06:00 [entrez]
PHST- 2015/03/04 06:00 [pubmed]
PHST- 2015/03/04 06:01 [medline]
PHST- 2014/05/22 00:00 [pmc-release]
AID - ofu018 [pii]
AID - 10.1093/ofid/ofu018 [doi]
PST - epublish
SO  - Open Forum Infect Dis. 2014 May 22;1(1):ofu018. doi: 10.1093/ofid/ofu018. 
      eCollection 2014 Mar.