A Common Genetic Variant in<i>FCGR3A</i>-V158F and Risk of Kaposi Sarcoma Herpesvirus Infection and Classic Kaposi Sarcoma

Brown, Elizabeth E.; Fallin, M. Daniele; Goedert, James J.; Chen, Renee; Whitby, Denise; Foster, Charles B.; Lauria, Carmela; Alberg, Anthony J.; Messina, Angelo; Montella, M.; Rezza, Giovanni; Vitale, Francesco; Chanock, Stephen J.

doi:10.1158/1055-9965.epi-04-0598

Cited by 17 publications

(9 citation statements)

References 49 publications

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“…We suspect that the differences in the two studies are due to chance and that analyzing data from a larger population would provide clarification. Interestingly, an allele dose response very similar to what we demonstrated for HIV-associated KS was also found in women, but not in men, with classical, non-HIV-associated KS (67).…”

Section: Discussionsupporting

confidence: 83%

FcγRIIa Genotype Predicts Progression of HIV Infection

Forthal

Landucci

Bream

et al. 2007

The Journal of Immunology

119

129

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Polymorphisms in FcγR genes are associated with susceptibility to or severity of a number of autoimmune and infectious diseases. We found that HIV-infected men in the Multicenter AIDS Cohort Study with the FcγRIIa RR genotype progressed to a CD4+ cell count of <200/mm3 at a faster rate than individuals with the RH or HH genotypes (relative hazard = 1.6; p = 0.0001). However, progression to AIDS (using the broad definition of either a CD4+ cell count <200/mm3 or development of an AIDS-defining illness) was less impacted by FcγRIIa genotype, largely because HH homozygotes had an increased risk of Pneumocystis jiroveci pneumonia as an AIDS-defining illness. We also showed that chronically infected subjects develop a substantial anti-gp120-specific IgG2 response. Moreover, HIV-1 immune complexes are more efficiently internalized by monocytes from HH subjects compared with RR subjects, likely because of the presence of IgG2 in the complexes. Finally, the FcγRIIIa F/V gene polymorphism was not associated with progression of HIV infection, but, as demonstrated previously, did predict the risk of Kaposi’s sarcoma. These results demonstrate the importance of FcγRs in AIDS pathogenesis and point toward a critical role for interactions between FcγRs and immune complexes in disease progression.

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Section: Discussionsupporting

confidence: 83%

FcγRIIa Genotype Predicts Progression of HIV Infection

Forthal

Landucci

Bream

et al. 2007

The Journal of Immunology

119

129

View full text Add to dashboard Cite

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“…The risk for Kaposi’s sarcoma (KS) in HIV-infected individuals was linked to NK cell-mediated ADCC via FCGR3A 158V polymorphism (44, 45), with the caveat that these studies predated the use of antiretroviral therapy and KS could have been a surrogate for HIV progression. Nonetheless, NK cell FCGR3A is a critical effector of ADCC and lysis of infected, inflammatory, and malignant cells.…”

Section: Discussionmentioning

confidence: 99%

Fc Gamma Receptor 3A Polymorphism and Risk for HIV-Associated Cryptococcal Disease

Rohatgi

Gohil

Kuniholm

et al. 2013

mBio

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Cryptococcus neoformans is one of the most common causes of fungal disease in HIV-infected persons, but not all of those who are infected develop cryptococcal disease (CD). Although CD4+ T cell deficiency is a risk factor for HIV-associated CD, polymorphisms of phagocytic Fc gamma receptors (FCGRs) have been linked to CD risk in HIV-uninfected persons. To investigate associations between FCGR2A 131 H/R and FCGR3A 158 F/V polymorphisms and CD risk in HIV-infected persons, we performed PCR-based genotyping on banked samples from 164 men enrolled in the Multicenter AIDS Cohort Study (MACS): 55 who were HIV infected and developed CD and a matched control group of 54 who were HIV infected and 55 who were HIV uninfected. Using additive and allelic statistical models for analysis, the high-affinity FCGR3A 158V allele was significantly associated with CD status after adjusting for race/ethnicity (odds ratio [OR], 2.1; P = 0.005), as was the FCGR3A 158 VV homozygous genotype after adjusting for race/ethnicity, rate of CD4+ T cell decline, and nadir CD4+ T cell count (OR, 21; P = 0.005). No associations between CD and FCGR2A 131 H/R polymorphism were identified. In binding studies, human IgG (hIgG)-C. neoformans complexes exhibited more binding to CHO-K1 cells expressing FCGR3A 158V than to those expressing FCGR3A 158F, and in cytotoxicity assays, natural killer (NK) cells expressing FCGR3A 158V induced more C. neoformans-infected monocyte cytotoxicity than those expressing FCGR3A 158F. Together, these results show an association between the FCGR3A 158V allele and risk for HIV-associated CD and suggest that this polymorphism could promote C. neoformans pathogenesis via increased binding of C. neoformans immune complexes, resulting in increased phagocyte cargo and/or immune activation.

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“…26 An association of the 158 V/F polymorphism with herpes family virus infections and oncogenesis has recently been documented, as the polymorphism influences the susceptibility to human herpesvirus-8 infection and HIV-associated Kaposi sarcoma. 27 No previous studies have investigated a possible influence of FCGR3A alleles on the immune response to EBV infection, nor on the survival after NHL in the absence of mAb treatment. Strikingly, despite a strong association of FCGR3A genotype with survival after lymphoma diagnosis, no association could be detected between this genetic locus and either EBV reactivation in control patients (data not shown) or incidence of lymphoma.…”

Section: Discussionmentioning

confidence: 99%