Effect of host genetics on the development of cytomegalovirus retinitis in patients with AIDS

Efe Sezgin; Douglas A. Jabs; Sher L. Hendrickson; Mark Van Natta; Alexander Zdanov; Richard Alan Lewis; Michael W. Smith; Jennifer L. Troyer; Stephen J. O'Brien

doi:10.1086/654814

Effect of host genetics on the development of cytomegalovirus retinitis in patients with AIDS

Efe Sezgin, Douglas A. Jabs, Sher L. Hendrickson, Mark Van Natta, Alexander Zdanov, Richard Alan Lewis, Michael W. Smith, Jennifer L. Troyer, Stephen J. O'Brien

Icahn School of Medicine at Mount Sinai

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

32 Scopus citations

Abstract

Background. Cytomegalovirus (CMV) retinitis is a common opportunistic infection among patients with AIDS and still causes visual morbidity despite the wide spread usage of highly active antiretroviral therapy (HAART). The ubiquitous CMV pathogen contains a human interleukin-10 (IL-10) homolog in its genome and utilizes it to evade host immune reactions through an IL-10 receptor mediated immune-suppression pathway. Methods. Effects of IL-10R1, IL-10 and previously described AIDS restriction gene variants are investigated on the development of CMV retinitis in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort (n = 1284). Results. In European Americans (n = 750), a haplotype carrying an amino acid changing variation in the cytoplasmic domain (S420L) of IL-10R1 can be protective (OR, 0.14; 95% CI, 0.02-0.94; P = .04) against, whereas another haplotype carrying an amino acid changing variation in the extracellular domain (I224V) of IL-10R1 can be more susceptible (OR, 6.21; 95% CI, 1.22- 31.54; P = .03) to CMV retinitis. In African Americans (n = 534), potential effects of IL-10 variants are observed. Conclusion. Host genetics may have a role in the occurrence of CMV retinitis in patients infected with HIV.

Original language	English
Pages (from-to)	606-613
Number of pages	8
Journal	Journal of Infectious Diseases
Volume	202
Issue number	4
DOIs	https://doi.org/10.1086/654814
State	Published - 15 Aug 2010

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@article{34b48e0be6c84d0b8bd4b8c7c081e009,

title = "Effect of host genetics on the development of cytomegalovirus retinitis in patients with AIDS",

abstract = "Background. Cytomegalovirus (CMV) retinitis is a common opportunistic infection among patients with AIDS and still causes visual morbidity despite the wide spread usage of highly active antiretroviral therapy (HAART). The ubiquitous CMV pathogen contains a human interleukin-10 (IL-10) homolog in its genome and utilizes it to evade host immune reactions through an IL-10 receptor mediated immune-suppression pathway. Methods. Effects of IL-10R1, IL-10 and previously described AIDS restriction gene variants are investigated on the development of CMV retinitis in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort (n = 1284). Results. In European Americans (n = 750), a haplotype carrying an amino acid changing variation in the cytoplasmic domain (S420L) of IL-10R1 can be protective (OR, 0.14; 95% CI, 0.02-0.94; P = .04) against, whereas another haplotype carrying an amino acid changing variation in the extracellular domain (I224V) of IL-10R1 can be more susceptible (OR, 6.21; 95% CI, 1.22- 31.54; P = .03) to CMV retinitis. In African Americans (n = 534), potential effects of IL-10 variants are observed. Conclusion. Host genetics may have a role in the occurrence of CMV retinitis in patients infected with HIV.",

author = "Efe Sezgin and Jabs, {Douglas A.} and Hendrickson, {Sher L.} and Natta, {Mark Van} and Alexander Zdanov and Lewis, {Richard Alan} and Smith, {Michael W.} and Troyer, {Jennifer L.} and O'Brien, {Stephen J.}",

note = "Funding Information: Financial support: This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health (contract HHSN261200800001E) and with cooperative agreements from the National Eye Institute, National Institutes of Health (grant U10-EY-08052 to the Mount Sinai School of Medicine, New York, NY; grant U10-EY-08057 to the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; and grant U10-EY-08067 to the University of Wisconsin, Madison).",

year = "2010",

month = aug,

day = "15",

doi = "10.1086/654814",

language = "English",

volume = "202",

pages = "606--613",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Effect of host genetics on the development of cytomegalovirus retinitis in patients with AIDS

AU - Sezgin, Efe

AU - Jabs, Douglas A.

AU - Hendrickson, Sher L.

AU - Natta, Mark Van

AU - Zdanov, Alexander

AU - Lewis, Richard Alan

AU - Smith, Michael W.

AU - Troyer, Jennifer L.

AU - O'Brien, Stephen J.

N1 - Funding Information: Financial support: This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health (contract HHSN261200800001E) and with cooperative agreements from the National Eye Institute, National Institutes of Health (grant U10-EY-08052 to the Mount Sinai School of Medicine, New York, NY; grant U10-EY-08057 to the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; and grant U10-EY-08067 to the University of Wisconsin, Madison).

PY - 2010/8/15

Y1 - 2010/8/15

N2 - Background. Cytomegalovirus (CMV) retinitis is a common opportunistic infection among patients with AIDS and still causes visual morbidity despite the wide spread usage of highly active antiretroviral therapy (HAART). The ubiquitous CMV pathogen contains a human interleukin-10 (IL-10) homolog in its genome and utilizes it to evade host immune reactions through an IL-10 receptor mediated immune-suppression pathway. Methods. Effects of IL-10R1, IL-10 and previously described AIDS restriction gene variants are investigated on the development of CMV retinitis in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort (n = 1284). Results. In European Americans (n = 750), a haplotype carrying an amino acid changing variation in the cytoplasmic domain (S420L) of IL-10R1 can be protective (OR, 0.14; 95% CI, 0.02-0.94; P = .04) against, whereas another haplotype carrying an amino acid changing variation in the extracellular domain (I224V) of IL-10R1 can be more susceptible (OR, 6.21; 95% CI, 1.22- 31.54; P = .03) to CMV retinitis. In African Americans (n = 534), potential effects of IL-10 variants are observed. Conclusion. Host genetics may have a role in the occurrence of CMV retinitis in patients infected with HIV.

AB - Background. Cytomegalovirus (CMV) retinitis is a common opportunistic infection among patients with AIDS and still causes visual morbidity despite the wide spread usage of highly active antiretroviral therapy (HAART). The ubiquitous CMV pathogen contains a human interleukin-10 (IL-10) homolog in its genome and utilizes it to evade host immune reactions through an IL-10 receptor mediated immune-suppression pathway. Methods. Effects of IL-10R1, IL-10 and previously described AIDS restriction gene variants are investigated on the development of CMV retinitis in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort (n = 1284). Results. In European Americans (n = 750), a haplotype carrying an amino acid changing variation in the cytoplasmic domain (S420L) of IL-10R1 can be protective (OR, 0.14; 95% CI, 0.02-0.94; P = .04) against, whereas another haplotype carrying an amino acid changing variation in the extracellular domain (I224V) of IL-10R1 can be more susceptible (OR, 6.21; 95% CI, 1.22- 31.54; P = .03) to CMV retinitis. In African Americans (n = 534), potential effects of IL-10 variants are observed. Conclusion. Host genetics may have a role in the occurrence of CMV retinitis in patients infected with HIV.

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U2 - 10.1086/654814

DO - 10.1086/654814

M3 - Article

C2 - 20617924

AN - SCOPUS:77954753596

SN - 0022-1899

VL - 202

SP - 606

EP - 613

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 4

ER -

Effect of host genetics on the development of cytomegalovirus retinitis in patients with AIDS

Abstract

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