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Common Genetic Variation and the Control of HIV-1 in Humans

2009; Public Library of Science; Volume: 5; Issue: 12 Linguagem: Inglês

10.1371/journal.pgen.1000791

1553-7404

Jacques Fellay, Dongliang Ge, Kevin V. Shianna, Sara Colombo, Bruno Ledergerber, Elizabeth T. Cirulli, Thomas Urban, Kunlin Zhang, Curtis Gumbs, Jason P. Smith, Antonella Castagna, Alessandro Cozzi‐Lepri, Andrea De Luca, Philippa Easterbrook, Huldrych F. Günthard, S. Mallal, Cristina Mussini, Judith Dalmau, Javier Martínez‐Picado, José M. Miró, Niels Obel, Steven M. Wolinsky, Jeremy Martinson, Roger Detels, Joseph B. Margolick, Lisa P. Jacobson, Patrick Descombes, Stylianos E. Antonarakis, J. Beckmann, Stephen J. O’Brien, Norman L. Letvin, Andrew J. McMichael, Barton F. Haynes, Mary Carrington, Sheng Feng, Amalio Telenti, David B. Goldstein,

Immune Cell Function and Interaction

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.