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PMID: 17641165 Published · ppublish English Journal Article Multicenter Study Research Support, Non-U.S. Gov't

A whole-genome association study of major determinants for host control of HIV-1.

Science (New York, N.Y.) ·Vol. 317 ·No. 5840 ·2007-08-17 ·Pages 944-7

Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M, Zhang K, Gumbs C, Castagna A, Cossarizza A, Cozzi-Lepri A, De Luca A, Easterbrook P, Francioli P, Mallal S, Martinez-Picado J, Miro JM, Obel N, Smith JP, Wyniger J, Descombes P, Antonarakis SE, Letvin NL, McMichael AJ, Haynes BF, Telenti A, Goldstein DB

Abstract

Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.

MeSH Terms
Cohort Studies DNA-Binding Proteins/genetics Disease Progression Female Genes, MHC Class I Genome, Human HIV Infections/genetics,immunology,therapy,virology HIV-1/physiology HLA-B Antigens/genetics HLA-C Antigens/genetics Haplotypes Humans Immediate-Early Proteins/genetics Major Histocompatibility Complex/genetics Male Polymorphism, Single Nucleotide RNA, Long Noncoding RNA, Untranslated Regression Analysis Viral Load
Chemicals
DNA-Binding Proteins HCP5 long noncoding RNA, human HLA-B Antigens HLA-B*57:01 antigen HLA-C Antigens Immediate-Early Proteins POLR1H protein, human RNA, Long Noncoding RNA, Untranslated RNF39 protein, human
Authors & Affiliations
27 authors, click to expand affiliations / ORCID
Fellay Jacques
Center for Population Genomics and Pharmacogenetics, Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27710, USA.
Shianna Kevin V
Ge Dongliang
Colombo Sara
Ledergerber Bruno
Weale Mike
Zhang Kunlin
Gumbs Curtis
Castagna Antonella
Cossarizza Andrea
Cozzi-Lepri Alessandro
De Luca Andrea
Easterbrook Philippa
Francioli Patrick
Mallal Simon
Martinez-Picado Javier
Miro José M
Obel Niels
Smith Jason P
Wyniger Josiane
Descombes Patrick
Antonarakis Stylianos E
Letvin Norman L
McMichael Andrew J
Haynes Barton F
Telenti Amalio
Goldstein David B
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1143767
Published
2007-08-17
Epub
2007-00-19
Pages
944-7
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC1991296
Subset
IM
Grants
Medical Research Council · G0200585 · United Kingdom
Medical Research Council · MC_U137884177 · United Kingdom
NIAID NIH HHS · U19 AI067854 · United States
NIAID NIH HHS · U19 AI067854-03 · United States
Corrections
CommentIn
PMID: 17947564
External Links
PubMed source DOI: 10.1126/science.1143767 PMC Full Text View journal details
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