The role of chemokine C-C motif ligand 2 genotype and cerebrospinal fluid chemokine C-C motif ligand 2 in neurocognition among HIV-infected patients.
Title | The role of chemokine C-C motif ligand 2 genotype and cerebrospinal fluid chemokine C-C motif ligand 2 in neurocognition among HIV-infected patients. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Thames, AD, Briones, MS, Magpantay, LI, Martinez-Maza, O, Singer, EJ, Hinkin, CH, Morgello, S, Gelman, BB, Moore, DJ, Heizerling, K, Levine, AJ |
Journal | AIDS |
Volume | 29 |
Issue | 12 |
Pagination | 1483-91 |
Date Published | 2015 Jul 31 |
ISSN | 1473-5571 |
Keywords | Adolescent, Adult, AIDS Dementia Complex, CD4 Lymphocyte Count, Cerebrospinal Fluid, Chemokine CCL2, Cross-Sectional Studies, Cytokines, Female, Genetic Predisposition to Disease, Genotype, HIV Infections, Humans, Internal, Male, Middle Aged, Neuropsychological Tests, Plasma, Viral Load, Young Adult |
Abstract | OBJECTIVES: We examined interrelationships between chemokine C-C motif ligand 2 (CCL2) genotype and expression of inflammatory markers in the cerebrospinal fluid (CSF), plasma viral load, CD4 cell count and neurocognitive functioning among HIV-infected adults. We hypothesized that HIV-positive carriers of the 'risk' CCL2 -2578G allele, caused by a single nucleotide polymorphism (SNP) at rs1024611, would have a higher concentration of CCL2 in CSF, and that CSF CCL2 would be associated with both higher concentrations of other proinflammatory markers in CSF and worse neurocognitive functioning.DESIGN: A cross-sectional study of 145 HIV-infected individuals enrolled in the National NeuroAIDS Tissue Consortium cohort for whom genotyping, CSF and neurocognitive data were available.METHODS: Genomic DNA was extracted from peripheral blood mononuclear cells and/or frozen tissue specimens. CSF levels of CCL2, interleukin (IL)-2, IL-6, tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), soluble tumor necrosis factor receptor 2, sIL-6Rα, sIL-2, sCD14 and B-cell activating factor were quantified. Neurocognitive functioning was measured using a comprehensive battery of neuropsychological tests.RESULTS: Carriers of the CCL2 -2578G allele had a significantly higher concentration of CCL2 in CSF. CSF CCL2 level was positively and significantly associated with other CSF neuroinflammatory markers and worse cognitive functioning. There was a significant association between genotype and plasma viral load, such that carriers of the CCL2 -2578G allele with high viral load expressed greater levels of CCL2 and had higher neurocognitive deficit scores than other genotype/viral load groups.CONCLUSION: Individuals with the CCL2 -2578G allele had higher levels of CCL2 in CSF, which was associated with increased pro-inflammatory markers in CSF and worse neurocognitive functioning. The results highlight the potential role of intermediate phenotypes in studies of genotype and cognition. |
DOI | 10.1097/QAD.0000000000000706 |
Alternate Journal | AIDS |
PubMed ID | 26244388 |
PubMed Central ID | PMC4573552 |
Grant List | U24MH100925 / MH / NIMH NIH HHS / United States U24 MH100929 / MH / NIMH NIH HHS / United States U24 MH100925 / MH / NIMH NIH HHS / United States U01 MH083500 / MH / NIMH NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States U24MH100928 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States U24MH100930 / MH / NIMH NIH HHS / United States U24MH100931 / MH / NIMH NIH HHS / United States R25 MH080663 / MH / NIMH NIH HHS / United States K23 MH095661 / MH / NIMH NIH HHS / United States U24MH100929 / MH / NIMH NIH HHS / United States R25 MH080661 / MH / NIMH NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States K23 MH096551 / MH / NIMH NIH HHS / United States |