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Determining the Role of Fc gamma Receptor (FCGR) gene polymorphisms in HIV infection progression and treatment outcomes in Ghanaian Adults

Determining the Role of Fc gamma Receptor (FCGR) gene polymorphisms in HIV infection progression and treatment outcomes in Ghanaian Adults

Project Lead(s)
DR. HELENA LAMPTEY - SENIOR RESEARCH FELLOW
Dr. Helena Lamptey
Senior Research Fellow
Project Background 

During HIV infection the host immune system elicits antibodies to control the virus. Depending on receptor type, Fc Gamma Receptors (FcγR) can regulate immunity by causing cell activation or inhibition in response to infections. There are differences in HIV infection progression and treatment outcomes among different patients. One of the factors hypothesized to be the cause of these differences is FCGR polymorphisms. Genetic variations that occur in FCGR genes such as Copy Number Variations (CNV) and Single Nucleotide Polymorphisms (SNPs) have been shown to affect Fc-mediated effector functions. These variations could modify FcR expression and IgG isotype binding, which would affect HIV infection risk and disease progression. Although the burden of HIV in Africa is high, data is lacking on the effect of FCGR polymorphisms on HIV disease progression and antiretroviral therapy (ART) response in African populations. Therefore, it is important to determine the impact of host FCGR polymorphisms on HIV infection progression and ART response in the Ghanaian population.

Objectives/Research Areas 
  1. To genotype FcγRIIa, FcγRIIb, FcγRIIc, FcγRIIIa and FcγRIIIb SNPs and copy number variants associated with HIV infection and treatment outcomes. 
  2. To measure the reservoir size of the patients (total HIV DNA, cell associated RNA). 
  3. To evaluate virological and immunological biomarkers of the HIV-1 latent reservoir.
Key Findings 

In this pilot study, single-nucleotide polymorphisms (SNPs) in FcγRIIIa, FcγRIIa, and FcγRIIb genes were determined by Sanger sequencing in 50 HIV-infected ART-suppressed individuals. HIV reservoir size was determined by quantifying total HIV DNA (vDNA) and cell-associated unspliced (US) HIV RNA by qPCR. Association analysis was performed using three coding SNPs, one per gene (FcγRIIIa-rs396991, FcγRIIa-rs1801274, and FcγRIIb-rs1050501).  

The median reservoir size as estimated by vDNA copy number was 116 (range, 1 – 5798) copies/million cells and US RNA was detectable in 15 out of the 50 samples. Our analysis found the reservoir size was almost 6 times larger in males compared to females who are suppressed. Reservoir size was observed to be larger in younger patients compared to those older, however, not statistically significant. However, there was no significant associations between the FcγR SNPs and HIV vDNA or US RNA. Studies in larger cohorts are necessary to explore associations between FcγR polymorphisms and HIV reservoir. 

Ongoing Activities  
  • FCGR genotyping in our H-CRIS cohort 
  • Determination of HIV reservoir size 
  • Evaluation of virological and immunological biomarkers of the HIV-1 latent reservoir 
Key Publications  

Lamptey, H., Bonney, E. Y., Adu, B., & Kyei, G. B. (2021). Are Fc Gamma Receptor Polymorphisms Important in HIV-1 Infection Outcomes and Latent Reservoir Size?. Frontiers in immunology, 12, 656894. https://doi.org/10.3389/fimmu.2021.656894 

Team 
Internal Collaborator(s) 
Dr. George B. Kyei
Dr. Evelyn Yayra Bonney
Dr. Bright Adu
External Collaborator(s) 
Dr. Alexander O. Pasternak, Professor Ben Berkhout, Dr. Philipp Adams (Amsterdam University Medical Centre, Laboratory of Experimental Virology, Amsterdam)
Funder(s) 
EDCTP-AREF preparatory fellowship TMA2018PF-2535