Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus

Efe Sezgin; Mark L. Van Natta; Alka Ahuja; Alice Lyon; Sunil Srivastava; Jennifer L. Troyer; Stephen J. O'Brien; Douglas A. Jabs

doi:10.1016/j.ajo.2010.11.029

Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus

Efe Sezgin^*, Mark L. Van Natta, Alka Ahuja, Alice Lyon, Sunil Srivastava, Jennifer L. Troyer, Stephen J. O'Brien, Douglas A. Jabs

^*Corresponding author for this work

Ophthalmology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

• Purpose: To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. • Design: Prospective, multicenter, observational study. • Methods: Cox proportional hazards model based genetic association tests examined the influence of IL-10R1-S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3′A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis. • Results: European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95% CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95% CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3′A variant (HR = 3.89; 95% CI: 1.42-10.60; P = .008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95% CI: 1.01-9.16; P = .05). • Conclusion: Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART.

Original language	English (US)
Pages (from-to)	999-1006.e4
Journal	American journal of ophthalmology
Volume	151
Issue number	6
DOIs	https://doi.org/10.1016/j.ajo.2010.11.029
State	Published - Jun 2011

Funding

Additional support provided by National Center for Research Resources through General Clinical Research Center grants: Supported by cooperative agreements from the National Eye Institute to The Johns Hopkins University School of Medicine (U10 EY 08052), The Johns Hopkins University Bloomberg School of Public Health (U10 EY 08057), and the University of Wisconsin, Madison School of Medicine (U10 EY 08067). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health.

ASJC Scopus subject areas

Ophthalmology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ajo.2010.11.029

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@article{5681bc7ee910496bb58860a6b9a659dd,

title = "Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus",

abstract = "• Purpose: To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. • Design: Prospective, multicenter, observational study. • Methods: Cox proportional hazards model based genetic association tests examined the influence of IL-10R1-S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3′A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis. • Results: European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95% CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95% CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3′A variant (HR = 3.89; 95% CI: 1.42-10.60; P = .008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95% CI: 1.01-9.16; P = .05). • Conclusion: Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART.",

author = "Efe Sezgin and {Van Natta}, {Mark L.} and Alka Ahuja and Alice Lyon and Sunil Srivastava and Troyer, {Jennifer L.} and O'Brien, {Stephen J.} and Jabs, {Douglas A.}",

note = "Funding Information: Additional support provided by National Center for Research Resources through General Clinical Research Center grants: Funding Information: Supported by cooperative agreements from the National Eye Institute to The Johns Hopkins University School of Medicine (U10 EY 08052), The Johns Hopkins University Bloomberg School of Public Health (U10 EY 08057), and the University of Wisconsin, Madison School of Medicine (U10 EY 08067). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health. ",

year = "2011",

month = jun,

doi = "10.1016/j.ajo.2010.11.029",

language = "English (US)",

volume = "151",

pages = "999--1006.e4",

journal = "American journal of ophthalmology",

issn = "0002-9394",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus

AU - Sezgin, Efe

AU - Van Natta, Mark L.

AU - Ahuja, Alka

AU - Lyon, Alice

AU - Srivastava, Sunil

AU - Troyer, Jennifer L.

AU - O'Brien, Stephen J.

AU - Jabs, Douglas A.

N1 - Funding Information: Additional support provided by National Center for Research Resources through General Clinical Research Center grants: Funding Information: Supported by cooperative agreements from the National Eye Institute to The Johns Hopkins University School of Medicine (U10 EY 08052), The Johns Hopkins University Bloomberg School of Public Health (U10 EY 08057), and the University of Wisconsin, Madison School of Medicine (U10 EY 08067). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health.

PY - 2011/6

Y1 - 2011/6

N2 - • Purpose: To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. • Design: Prospective, multicenter, observational study. • Methods: Cox proportional hazards model based genetic association tests examined the influence of IL-10R1-S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3′A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis. • Results: European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95% CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95% CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3′A variant (HR = 3.89; 95% CI: 1.42-10.60; P = .008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95% CI: 1.01-9.16; P = .05). • Conclusion: Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART.

AB - • Purpose: To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. • Design: Prospective, multicenter, observational study. • Methods: Cox proportional hazards model based genetic association tests examined the influence of IL-10R1-S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3′A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis. • Results: European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95% CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95% CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3′A variant (HR = 3.89; 95% CI: 1.42-10.60; P = .008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95% CI: 1.01-9.16; P = .05). • Conclusion: Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART.

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Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus

Abstract

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UN SDGs

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