Identifying Safety Concerns from Genetic Data: Lessons from the Development of CCR5 Inhibitors

Roses A.D. Pharmacogenetics and drug development: the path to safer and more effective drugs. Nat Rev Genet 2004; 5: 645–656.

Sabeti P.C. , Walsh E. , Schaffner S.F. The case for selection at CCR5–A32. PLoS Biol 2005; 3: e378.

Lederman M.M. , Penn-Nicholson A. , Cho M. , Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA 2006; 296: 815–826.

Khan I.A. , Thomas S.Y. , Moretto M.M. CCR5 is essential for NK cell trafficking and host survival following Toxoplasma gondii infection. PLoS Pathog 2006; 2: e49.

Glass W.G. , Lim J.K. , Cholera R. , Pletnev A.G. , Gao J.L. , Murphy P.M. Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection. J Exp Med 2005; 202: 1087–1098.

Rahbar R. , Murooka T.T. , Hinek A.A. Vaccinia virus activation of CCR5 invokes tyrosine phosphorylation signaling events that support virus replication. J Virol 2006; 80: 7245–7259.

Floto R.A. , MacAry P.A. , Boname J.M. Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5. Science 2006; 314: 454–458.

Ank N. , Petersen K. , Malmgaard L. , Mogensen S.C. , Paludan S.R. Age-dependent role for CCR5 in antiviral host defense against herpes simplex virus type 2. J Virol 2005; 79: 9831–9841.

Machado F.S. , Koyama N.S. , Carregaro V. CCR5 plays a critical role in the development of myocarditis and host protection in mice infected with Trypanosoma cruzi. J Infect Dis 2005; 191: 627–636.

Belnoue E. , Kayibanda M. , Deschemin J.C. CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood 2003; 101: 4253–4259.

Abel L. , Casanova J.L. Human genetics of infectious diseases: fundamental insights from clinical studies. Semin Immunol 2006; 18: 327–329.

Picard C. , Casanova J.L. , Abel L. Mendelian traits that confer predisposition or resistance to specific infections in humans. Curr Opin Immunol 2006; 18: 383–390.

Casrouge A. , Zhang S.Y. , Eidenschenk C. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 2006; 314: 308–312.

Gardam M.A. , Keystone E.C. , Menzies R. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003; 3: 148–155.

Prahalad S. Negative association between the chemokine receptor CCR5-δ32 polymorphism and rheumatoid arthritis: a meta-analysis. Genes Immun 2006; 7: 264–268.

Crabb C. GlaxoSmithKline ends aplaviroc trials. AIDS 2006; 20: 641.

Schlesselman J.J. Case-Control Studies: Design, Conduct, Analysis. 1982; pp. 69–81. Oxford: Oxford University Press.

Gonzalez E. , Dhanda R. , Bamshad M. Global survey of genetic variation in CCR5, RANTES, and MIP-1-α: impact on the epidemiology of the HIV-1 pandemic. PNAS 2001; 98: 5199–5204.

Deng H.W. Population admixture may appear to mask, change or reverse genetic effects of genes underlying complex traits. Genetics 2001; 159: 1319–1323.

Glass W.G. , McDermott D.H. , Lim J.K. CCR5 deficiency increases risk of symptomatic West Nile virus infection. J Exp Med 2006; 203: 35–40.

Thio C.L. , Astemborski J. , Bashirova A. Genetic protection against HBV conferred by CCR5 A32: evidence that CCR5 contributes to viral persistence. J Virol 2006; 81: 441–445.

Egger M. , Davey Smith G. , Altman D (Editors). Systematic Reviews in Health Care: Meta-analysis in Context. 2nd edn 2001; pp. 211–227. London: BMJ Books.