Effect of host genetics on incidence of HIV neuroretinal disorder in patients with AIDS.
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 CCR5Delta32, 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.
Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA. sezginef@mail.nih.gov
Efe
E
Sezgin
Sher L
SL
Hendrickson
Douglas A
DA
Jabs
Mark L
ML
Van Natta
Richard A
RA
Lewis
Jennifer L
JL
Troyer
Stephen J
SJ
O'Brien
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000235:genetics*; D000328:Adult; D018791:CD4 Lymphocyte Count; D018946:Chemokine CCL5 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D054390:Receptors, CCR2 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D015183:Restriction Mapping; D012164:Retinal Diseases / Q000453:epidemiology / Q000235:genetics / Q000821:virology*; D019562:Viral Load; D044465:White People
C483024:CCL5 protein, human; C515334:CCR2 protein, human; D018946:Chemokine CCL5; D054390:Receptors, CCR2; D019713:Receptors, CCR5