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

被引：331

作者：

Fellay, Jacques ^{[1
]}

Ge, Dongliang ^{[1
]}

Shianna, Kevin V. ^{[1
,2
]}

Colombo, Sara ^{[3
]}

Ledergerber, Bruno ^{[4
]}

Cirulli, Elizabeth T. ^{[1
]}

Urban, Thomas J. ^{[1
]}

Zhang, Kunlin ^{[3
,5
]}

Gumbs, Curtis E. ^{[1
]}

Smith, Jason P. ^{[2
]}

Castagna, Antonella ^{[6
]}

Cozzi-Lepri, Alessandro ^{[7
]}

De Luca, Andrea ^{[8
]}

Easterbrook, Philippa ^{[9
,10
,11
]}

Guenthard, Huldrych F. ^{[4
]}

Mallal, Simon ^{[12
,13
]}

Mussini, Cristina ^{[14
]}

Dalmau, Judith ^{[15
,16
]}

Martinez-Picado, Javier ^{[15
,16
,17
]}

Miro, Jose M. ^{[18
]}

Obel, Niels ^{[19
]}

Wolinsky, Steven M. ^{[20
]}

Martinson, Jeremy J. ^{[21
]}

Detels, Roger ^{[22
]}

Margolick, Joseph B. ^{[23
]}

Jacobson, Lisa P. ^{[24
]}

Descombes, Patrick ^{[25
]}

Antonarakis, Stylianos E. ^{[26
]}

Beckmann, Jacques S. ^{[27
,28
]}

O'Brien, Stephen J. ^{[29
]}

Letvin, Norman L. ^{[30
]}

McMichael, Andrew J. ^{[31
]}

Haynes, Barton F. ^{[32
]}

Carrington, Mary ^{[33
,34
]}

Feng, Sheng ^{[1
]}

Telenti, Amalio ^{[3
]}

Goldstein, David B. ^{[1
]}

机构：

[1] Duke Univ, Ctr Human Genome Variat, Duke Inst Genome Sci & Policy, Durham, NC 27706 USA

[2] Duke Univ, Genom Anal Facil, Duke Inst Genome Sci & Policy, Durham, NC USA

[3] Univ Lausanne, Inst Microbiol, Lausanne, Switzerland

[4] Univ Zurich, Univ Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland

[5] Chinese Acad Sci, Inst Psychol, Behav Genet Ctr, Beijing 100101, Peoples R China

[6] Vita Salute San Raffaele Univ & Diagnost & Ric Sa, Clin Infect Dis, Milan, Italy

[7] UCL, Res Dept Infect & Populat Hlth, London, England

[8] Univ Cattolica Sacro Cuore, Inst Clin Infect Dis, I-00168 Rome, Italy

[9] Kings Coll London, Acad Dept HIV GUM, Weston Educ Ctr, Guys Hosp, London WC2R 2LS, England

[10] Kings Coll London, Acad Dept HIV GUM, Weston Educ Ctr, Kings Hosp, London WC2R 2LS, England

[11] Kings Coll London, Acad Dept HIV GUM, St Thomas Hosp, Weston Educ Ctr, London, England

[12] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Inst Immunol & Infect Dis, Perth, WA, Australia

[13] Murdoch Univ, Perth, WA, Australia

[14] Azienda Osped Univ, Infect Dis Clin, Modena, Italy

[15] IrsiCaixa Fdn, Badalona, Spain

[16] Hosp Badalona Germans Trias & Pujol, Badalona, Spain

[17] ICREA, Barcelona, Spain

[18] Univ Barcelona, Hosp Clin, IDIBAPS, Barcelona, Spain

[19] Univ Copenhagen Hosp, Rigshosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark

[20] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA

[21] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA

[22] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[23] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA

[24] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[25] Univ Geneva, Natl Ctr Competence Res Frontiers Genet, Geneva, Switzerland

[26] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland

[27] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[28] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland

[29] NCI, Lab Genom Divers, Frederick, MD 21701 USA

[30] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA

[31] John Radcliffe Hosp, MRC, Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, England

[32] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA

[33] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA

[34] Massachusetts Gen Hosp, Ragon Inst, MIT& Harvard, Boston, MA 02114 USA

来源：

PLOS GENETICS | 2009年 / 5卷 / 12期

基金：

美国国家卫生研究院; 瑞士国家科学基金会;

关键词：

GENOME-WIDE ASSOCIATION; HLA-C; HOST GENETICS; INFECTION; POLYMORPHISM; PROGRESSION; RESISTANCE; HCP5; AIDS; INDIVIDUALS;

D O I：

10.1371/journal.pgen.1000791

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：12

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