The FCGR2C allele that modulated the risk of HIV-1 infection in the Thai RV144 vaccine trial is implicated in HIV-1 disease progression

Ria Lassaunière, Maria Paximadis, Osman Ebrahim, Richard E Chaisson, Neil A. Martinson, Caroline T. Tiemessen

Research output: Contribution to journalArticle

Abstract

In the HIV-1 Thai RV144 vaccine trial—the only trial to demonstrate any vaccine efficacy to date—a three-variant haplotype within the Fc gamma receptor 2C gene (FCGR2C) modified the risk of HIV-1 acquisition. A similar vaccine regimen is currently being evaluated in South Africa in the HVTN702 trial, where the predominant population is polymorphic for only a single variant in the haplotype, c.134-96C>T. To investigate the significance of c.134-96C>T in HIV-specific immunity in South Africans, this study assessed its role in HIV-1 disease progression. In a cohort of HIV-1-infected South African controllers (n = 71) and progressors (n = 73), the c.134-96C>T minor allele significantly associated with increased odds of HIV-1 disease progression (odds ratio 3.80, 95% confidence interval 1.90–7.62; P = 2.0 × 10–4, PBonf = 2.4 × 10–3). It is unlikely that the underlying mechanism involves wild-type FcγRIIc function, since only a single study participant was predicted to express wild-type FcγRIIc as determined by the FCGR2C c.798+1A>G splice-site variant. Conversely, in silico analysis revealed a potential role for c.134-96C> T in modulating mRNA transcription. In conclusion, these data provide additional evidence towards a role for FCGR2C c.134-96C>T in the context of HIV-1 and underscore the need to investigate its significance in the HVTN702 efficacy trial in South Africa.

Original languageEnglish (US)
JournalGenes and Immunity
DOIs
StateAccepted/In press - Jan 1 2018

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IgG Receptors
HIV Infections
Disease Progression
HIV-1
Vaccines
Alleles
Genes
South Africa
Haplotypes
Computer Simulation
Immunity
Odds Ratio
HIV
Confidence Intervals
Messenger RNA
Population

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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The FCGR2C allele that modulated the risk of HIV-1 infection in the Thai RV144 vaccine trial is implicated in HIV-1 disease progression. / Lassaunière, Ria; Paximadis, Maria; Ebrahim, Osman; Chaisson, Richard E; Martinson, Neil A.; Tiemessen, Caroline T.

In: Genes and Immunity, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "In the HIV-1 Thai RV144 vaccine trial—the only trial to demonstrate any vaccine efficacy to date—a three-variant haplotype within the Fc gamma receptor 2C gene (FCGR2C) modified the risk of HIV-1 acquisition. A similar vaccine regimen is currently being evaluated in South Africa in the HVTN702 trial, where the predominant population is polymorphic for only a single variant in the haplotype, c.134-96C>T. To investigate the significance of c.134-96C>T in HIV-specific immunity in South Africans, this study assessed its role in HIV-1 disease progression. In a cohort of HIV-1-infected South African controllers (n = 71) and progressors (n = 73), the c.134-96C>T minor allele significantly associated with increased odds of HIV-1 disease progression (odds ratio 3.80, 95{\%} confidence interval 1.90–7.62; P = 2.0 × 10–4, PBonf = 2.4 × 10–3). It is unlikely that the underlying mechanism involves wild-type FcγRIIc function, since only a single study participant was predicted to express wild-type FcγRIIc as determined by the FCGR2C c.798+1A>G splice-site variant. Conversely, in silico analysis revealed a potential role for c.134-96C> T in modulating mRNA transcription. In conclusion, these data provide additional evidence towards a role for FCGR2C c.134-96C>T in the context of HIV-1 and underscore the need to investigate its significance in the HVTN702 efficacy trial in South Africa.",
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