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Copy number variation of Fc gamma receptor genes in HIV-infected and HIV-tuberculosis co-infected individuals in Sub-Saharan Africa

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posted on 13.11.2013, 13:03 by Lee R. Machado, Jennifer Bowdrey, Eliford Ngaimisi, Abiy Habtewold, Omary Minzi, Eyasu Makonnen, Getnet Yimer, Wondwossen Amogne, Sabina Mugusi, Mohammed Janabi, Getachew Aderaye, Ferdinand Mugusi, Maria Viskaduraki, Eleni Aklillu, Edward J. Hollox
AIDS, caused by the retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa yet almost all genetic studies have focused on cohorts from Western countries. HIV shows high co-morbidity with tuberculosis (TB), as HIV stimulates the reactivation of latent tuberculosis (TB). Recent clinical trials suggest that an effective anti-HIV response correlates with non-neutralising antibodies. Given that Fcγ receptors are critical in mediating the non-neutralising effects of antibodies, analysis of the extensive variation at Fcγ receptor genes is important. Single nucleotide variation and copy number variation (CNV) of Fcγ receptor genes affects the expression profile, activatory/ inhibitory balance, and IgG affinity of the Fcγ receptor repertoire of each individual. In this study we investigated whether CNV of FCGR2C, FCGR3A and FCGR3B as well as the HNA1 allotype of FCGR3B is associated with HIV load, response to highly-active antiretroviral therapy (HAART) and co-infection with TB. We confirmed an effect of TB-co-infection status on HIV load and response to HAART, but no conclusive effect of the genetic variants we tested. We observed a small effect, in Ethiopians, of FCGR3B copy number, where deletion was more frequent in HIV-TB co-infected patients than those infected with HIV alone.

Funding

This work was supported by the Wellcome Trust [grant number 087663] and a United Kingdom Medical Research Council New Investigator award [grant number GO801123] to E.J.H.; European & Developing Countries Clinical Trials Partnership [grant numbers CT.2005.32030.001, CG_TA.05.40204_005]; and the Swedish International Development Cooperation Agency/ Department for Research Cooperation [grant numbers HIV-2006-031, SWE 2007–270, VR 521-2011-3437]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Citation

PLoS ONE, 2013, 8 (11), e78165

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VoR (Version of Record)

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PLoS ONE

Publisher

Public Library of Science

eissn

1932-6203

Copyright date

2013

Available date

13/11/2013

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http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078165

Language

en

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