title: Identification of Genes Whose Expression Profile Is Associated with Non-Progression towards AIDS Using eQTLs.
abstract: BACKGROUND
  Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS) and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS.
  
  
  METHODS
  We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs) involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs) that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate.
  
  
  RESULTS
  Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%). Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV.
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Spadoni
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Rucart
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Le Clerc
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands; Crucell Holland B.V., Archimedesweg 4-6, 2333 CN, Leiden, The Netherlands.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: van Manen
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Coulonges
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ulveling
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Laville
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Taoufik
authors.initials: T
authors.lastname: Labib
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Lieng
authors.initials: L
authors.lastname: Taing
authors.affiliation: Département de Génétique et Développement, Faculté de Médecine, Université de Genève, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Delaneau
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Montes
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands; Crucell Holland B.V., Archimedesweg 4-6, 2333 CN, Leiden, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Josselin
authors.initials: J
authors.lastname: Noirel
authors.affiliation: Chaire de Bioinformatique; Laboratoire Génomique, Bioinformatique, et Applications (EA 4627), Conservatoire National des Arts et Métiers, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D030541:Databases, Genetic; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics; D040641:Quantitative Trait Loci; D011897:Random Allocation; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome
chemical_list: D004268:DNA-Binding Proteins; C494649:DNAJB12 protein, human; D050956:HSP40 Heat-Shock Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C531063:ZFP57 protein, human; D011755:Pyrophosphatases; C491470:ENTPD4 protein, human