| Publication Abstract Display | | Type: Published Abstract | | Title: Role of genetic variants of chemokines, chemokine receptors and interleukin 4 promoter in HIV-1 related CNS impairment. | | Authors: Singh K, Marquie-Beck J, Ellis R, Letendre S, Woods S, Spector S | | Year: 2002 | | Publication: Conference on Viral & Host Genetic Factors Regulating HIV/CNS Disease, Washington, DC, Nov. 20-22 | | Volume: Issue: Pages: | | Abstract:Objective: To evaluate the potential impact of host genetic factors on the development of HIV-related neurological disease, we studied common DNA sequence variations (polymorphisms) in the genes coding for selected chemokines, chemokine receptors and the IL-4 promoter.
Methods: Subjects were 118 HIV-1 infected adults aged 19-55 years, enrolled in a prospective study of the neurological complications of HIV. Total DNA was extracted from PBMCs using a Qiagen DNA extraction kit. Single nucleotide polymorphisms (SNPs) and one deletion mutation were ascertained by real-time fluorescence assays with melting curve analysis using a LightCycler. The following specific genotypes were studied: CCR5-delta 32, CCR5-59029-G/A, CCR5-59353-T/C, CCR5-59356-C/T, CCR2-64I, SDF1-3´A, CX3CR1-745-G/A, CX3CR1-849-C/T, and IL4–589-C/T. Neurocognitive status at baseline and follow-up was assessed by comprehensive neuropsychological testing. AIDS was designated according to established clinical criteria (CDC, 1992). HIV RNA levels were measured using the Roche Amplicor ® assay.
Results: CCR5-delta 32 heterozygotes had lower CSF HIV RNA levels than wild type homozygotes (2.2 vs. 3.0 log10 copies/mL; p=0.02). Similarly, CX3CR1-849-T heterozygotes had lower CSF HIV RNA levels than C/C homozygotes (2.4 vs. 3.0 log10 copies/mL; p=0.03). No T/T homozygotes were observed. CSF RNA also tended to be lower in patients with the IL4–589-T allele than in those with C/C genotype (2.6 vs.2.97 log10 copies/mL; p=0.10). Progression to neurocognitive impairment during follow-up was not significantly related to any of the polymorphisms studied. Trends for faster progression to AIDS were observed in association with the CCR5-wt/wt and SDF1-3´A polymorphisms.
Conclusions: CCR5-wt/D32, CX3CR1-849-C/T and IL4–589-C/T polymorphisms showed potential associations with reduction in CSF viral load; however, we found no clear evidence that polymorphisms in chemokine receptor, chemokine or cytokine genes influence susceptibility to neurocognitive impairment. Because the number of subjects studied in this preliminary report was relatively small, larger cohorts of HIV-1 infected patients will be required to determine fully the role of chemokine receptor, chemokine and cytokine polymorphisms in HIV-1 related CNS impairment. |
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