TY - JOUR
T1 - Effect of host genetics on incidence of HIV neuroretinal disorder in patients with AIDS
AU - Sezgin, Efe
AU - Hendrickson, Sher L.
AU - Jabs, Douglas A.
AU - Van Natta, Mark L.
AU - Lewis, Richard A.
AU - Troyer, Jennifer L.
AU - O'Brien, Stephen J.
PY - 2010/8/1
Y1 - 2010/8/1
N2 - Approximately 10%-15% of patients with AIDS but without ocular opportunistic infections will have a presumed neuroretinal disorder (HIV-NRD), manifested by reduced contrast sensitivity and abnormal visual fields. The loss of contrast sensitivity often is sufficient to impair reading speed. To evaluate the effect of host genetics on HIV-NRD, we explored validated AIDS restriction gene variants CCR5Δ32, CCR2-64I, CCR5 P1, SDF-3'A, IL-10-5'A, RANTES-403A, RANTES-28G, RANTES-In1.1C, CX3CR1-249I, CX3CR1-280M, IFNG-179T, MDR1-3435T, and MCP-1364G, each of which has been implicated previously to influence HIV-1 infection, AIDS progression, therapy response, and antiviral drug metabolism, and an IL-10 receptor gene, IL-10R1, in the Longitudinal Study of the Ocular Complications of AIDS cohort. In European Americans (cases = 55, controls = 290), IL-10-5'A variant and its promoter haplotype (hazard ratio = 2.09, confidence interval. 1.19 to 3.67, P = 0.01), in African Americans (cases = 54, controls = 180), RANTES-In1.1C and the associated haplotype (hazard ratio = 2.72, confidence interval.: 1.48 to 5.00, P = 0.001), showed increased HIV-NRD susceptibility. Although sample sizes are small and P values do not pass a strict Bonferroni correction, our results suggest that, in European Americans, an IL-10-related pathway, and, in African Americans, chemokine receptor ligand polymorphisms in RANTES are risk factors for HIV-NRD development. Clearly, further studies are warrented.
AB - Approximately 10%-15% of patients with AIDS but without ocular opportunistic infections will have a presumed neuroretinal disorder (HIV-NRD), manifested by reduced contrast sensitivity and abnormal visual fields. The loss of contrast sensitivity often is sufficient to impair reading speed. To evaluate the effect of host genetics on HIV-NRD, we explored validated AIDS restriction gene variants CCR5Δ32, CCR2-64I, CCR5 P1, SDF-3'A, IL-10-5'A, RANTES-403A, RANTES-28G, RANTES-In1.1C, CX3CR1-249I, CX3CR1-280M, IFNG-179T, MDR1-3435T, and MCP-1364G, each of which has been implicated previously to influence HIV-1 infection, AIDS progression, therapy response, and antiviral drug metabolism, and an IL-10 receptor gene, IL-10R1, in the Longitudinal Study of the Ocular Complications of AIDS cohort. In European Americans (cases = 55, controls = 290), IL-10-5'A variant and its promoter haplotype (hazard ratio = 2.09, confidence interval. 1.19 to 3.67, P = 0.01), in African Americans (cases = 54, controls = 180), RANTES-In1.1C and the associated haplotype (hazard ratio = 2.72, confidence interval.: 1.48 to 5.00, P = 0.001), showed increased HIV-NRD susceptibility. Although sample sizes are small and P values do not pass a strict Bonferroni correction, our results suggest that, in European Americans, an IL-10-related pathway, and, in African Americans, chemokine receptor ligand polymorphisms in RANTES are risk factors for HIV-NRD development. Clearly, further studies are warrented.
KW - AIDS
KW - HIV-1
KW - HIV-neuroretinal disorder
KW - host genetics
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U2 - 10.1097/QAI.0b013e3181deaf4d
DO - 10.1097/QAI.0b013e3181deaf4d
M3 - Article
C2 - 20531015
AN - SCOPUS:77955483527
SN - 1525-4135
VL - 54
SP - 343
EP - 351
JO - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
JF - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
IS - 4
ER -