Common genetic variation and the control of HIV-1 in humans
| Autor: | Barton F. Haynes, Antonella Castagna, Kevin V. Shianna, Andrew J. McMichael, Simon Mallal, Curtis Gumbs, Steven M. Wolinsky, Huldrych F. Günthard, Joseph B. Margolick, Stylianos E. Antonarakis, Norman L. Letvin, Jacques S. Beckmann, Lisa P. Jacobson, David Goldstein, Jeremy J. Martinson, Andrea De Luca, Amalio Telenti, Stephen J. O'Brien, Roger Detels, Mary Carrington, Patrick Descombes, Sara Colombo, Kunlin Zhang, José M. Miró, Judith Dalmau, Niels Obel, Cristina Mussini, Bruno Ledergerber, Javier Martinez-Picado, Alessandro Cozzi-Lepri, Thomas J. Urban, Elizabeth T. Cirulli, Dongliang Ge, Jason Smith, Jacques Fellay, Philippa J. Easterbrook, Sheng Feng |
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| Přispěvatelé: | University of Zurich, Fellay, J, McCarthy, Mark I, Universitat de Barcelona, NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI), Fellay, Jacque, Ge, Dongliang, Shianna Kevin, V., Colombo, Sara, Ledergerber, Bruno, Cirulli Elizabeth, T., Urban Thomas, J., Zhang, Kunlin, Gumbs Curtis, E., Smith Jason, P., Castagna, Antonella, Cozzi Lepri, Alessandro, De Luca, Andrea, Easterbrook, Philippa, Guenthard Huldrych, F., Mallal, Simon, Mussini, Cristina, Dalmau, Judith, Martinez Picado, Javier, Miro Jose, M., Obel, Niel, Wolinsky Steven, M., Martinson Jeremy, J., Detels, Roger, Margolick Joseph, B., Jacobson Lisa, P., Descombes, Patrick, Antonarakis Stylianos, E., Beckmann Jacques, S., O'Brien Stephen, J., Letvin Norman, L., McMichael Andrew, J., Haynes Barton, F., Carrington, Mary, Feng, Sheng, Telenti, Amalio, Goldstein David, B., Antonarakis, Stylianos |
| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research Candidate gene genetic control Genome-wide association study HIV Infections Human genetic variation Kaplan-Meier Estimate Major Histocompatibility Complex/genetics 10234 Clinic for Infectious Diseases Major Histocompatibility Complex 2.1 Biological and endogenous factors ddc:576.5 1306 Cancer Research Molecular genetics Aetiology Genetics (clinical) Genetics and Genomics/Genetics of Disease Genetics HIV-1/ physiology Single Nucleotide Infectious Diseases/HIV Infection and AIDS Viral Load Polymorphism Single Nucleotide/genetics HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) CD4(+) cells Infectious Diseases Phenotype Adult Alleles Disease Progression Female Genetic Variation Genotype HIV Infections/virology HIV-1/physiology Humans HIV/AIDS Infection Research Article medicine.medical_specialty 2716 Genetics (clinical) lcsh:QH426-470 Single-nucleotide polymorphism 610 Medicine & health Biology Genetics and Genomics/Complex Traits Polymorphism Single Nucleotide Genètica molecular 1311 Genetics Clinical Research Genetic variation medicine VIH (Virus) 1312 Molecular Biology Allele Polymorphism Molecular Biology Ecology Evolution Behavior and Systematics Kaplan-Meiers Estimate HIV (Viruses) Haplotype Human Genome HIV Virology/Mechanisms of Resistance and Susceptibility including Host Genetics NIAID Center for HIV/AIDS Vaccine Immunology lcsh:Genetics 1105 Ecology Evolution Behavior and Systematics HIV-1 Immunology/Genetics of the Immune System Developmental Biology |
| Zdroj: | PLoS genetics, vol 5, iss 12 Dipòsit Digital de la UB Universidad de Barcelona PLoS Genetics, Vol 5, Iss 12, p e1000791 (2009) Recercat. Dipósit de la Recerca de Catalunya instname PLoS genetics, vol. 5, no. 12, pp. e1000791 PLoS Genetics PLOS Genetics, Vol. 5, No 12 (2009) P. e1000791 |
| ISSN: | 1553-7390 |
| Popis: | To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians. Author Summary The ability to spontaneously control HIV-1 upon infection is highly variable between individuals. To evaluate the contribution of variation in human genes to differences in plasma viral load and in disease progression rates, we performed a genome-wide association study in >2,500 HIV–infected individuals. This study achieved two goals: it completed the analysis of common variation influencing viral control, and it re-assessed the majority of previously reported genetic associations. We show that genetic variants located near the HLA-B and HLA-C genes are the strongest determinants of viral control, and that other independent associations exist in the same region of chromosome 6, the Major Histocompatibility Complex, known to contain a large number of genes involved in immune defense. We could not replicate most of the previously published associations with HIV candidate genes in this large, well-characterized cohort. Overall, common human genetic variation, together with demographic variables, explains up to 22% of the variability in viral load in the Caucasian population. |
| Databáze: | OpenAIRE |
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