| Publication Abstract Display | | Type: Published Abstract | | Title: Apolipoprotein E (APOE) and mannose binding lectin 2 (MBL2) O/O genotypes are associated with neurocognitive impairment in HIV-infected former plasma donors from Anhui Province, China. | | Authors: Spector S, Singh K, Gupta S, Cysique L, Jin H, Letendre S, Schrier R, Wu Z, Hong K, Heaton R, and the HNRC Group | | Year: 2010 | | Publication: 17th Conference on Retroviruses and Opportunistic Infections | | Volume: Issue: Pages: | | Abstract:Background: Host genetic factors are important determinants for risk of HIV infection and disease progression. This study examined the association between host genetics and neurocognitive impairment in a population of Chinese infected through contact with contaminated blood products.
Methods: Extensive neuropsychological testing was performed on 203 HIV-infected persons from Anhui, China, at baseline and at 12 months. DNA extracted from dried blood spots were genotyped for APOE ε2, ε3, and ε4 alleles, MBL2-A/O,CCR5-wt/Δ32, CCR5-59029-G/A, CCR2-180-G/A, SDF-1-G/A, IL4-589-C/T, MCP-1-2518-A/G, CX3CR1-745-G/A, -849-C/T polymorphisms and CCL3L1 copy number variants using real-time polymerase chain reaction (PCR). Categorical variables were compared using either the c2 test or Fishers exact test.
Results: The cohort was 61% male, mean education = 5.5 years, AIDS diagnosis 113 (55%), on ART 114 (56%), mean baseline CD4+ count: 349/mm3, and mean log10 RNA 4.09. At baseline, 37% of subjects were impaired on neuropsychological testing (≥0.5 Global Deficit Score) increasing to 44% at 12-month follow-up. Of subjects with the APOE ε4 allele, 58% were cognitively impaired compared to 31% without the ε4 allele (P =0.001, OR = 3.09; 95%CI 1.54 to 6.18). The increased impairment held whether subjects were on ART (P =0.042, OR = 2.64; 95%CI 1.04 to 6.68) or not (P =0.018, OR = 3.75; 95%CI 1.28 to 10.99). The associations between ε4 genotypes held in multivariate analyses controlling for CD4+ count, HIV viral load, or both. Additionally, although there was no association with APOE alleles for the entire cohort at 12 months, 70% of ε4 positive vs 42% ε4 negative subjects on treatment at baseline and at 12 months were cognitively impaired (P =0.032, OR = 3.12; 95%CI 1.15 to 3.12). For MBL2 genotypes at baseline, no significant differences were observed. However, whereas 52% of subjects with the O/O genotype declined in cognitive function over 12 months, only 23% of subjects in the A/A group had declining cognition (OR = 3.62. 95%CI 1.46 to 9.03; P =0.0042). This association held in multivariate analyses controlling for CD4+ count, viral load, or both. No associations were observed for any of the other genetic variants evaluated.
Conclusions: The ApoE ε4 allele was associated with increased risk for cognitive deficits in people infected with HIV in China at baseline independent of viral load, CD4+ count or ART, while the MBL2 O/O genotype was associated with an increased risk for cognitive decline. |
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