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.

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.

• Authors: April D Thames, Marisa S Briones, Larry I Magpantay, Otoniel Martinez-Maza, Elyse J Singer, Charles H Hinkin, Susan Morgello, Benjamin B Gelman, David J Moore, Keith Heizerling, Andrew J Levine
• Journal: AIDS (London, England) (AIDS) Vol. 29 Issue 12 Pg. 1483-91 (Jul 31 2015) ISSN: 1473-5571 [Electronic] England
• PMID: 26244388 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CCL2 protein, human
• Chemokine CCL2
• Cytokines

Topics

• AIDS Dementia Complex (pathology)
• Adolescent
• Adult
• CD4 Lymphocyte Count
• Cerebrospinal Fluid (chemistry)
• Chemokine CCL2 (genetics)
• Cross-Sectional Studies
• Cytokines (cerebrospinal fluid)
• Female
• Genetic Predisposition to Disease
• Genotype
• HIV Infections (pathology)
• Humans
• Male
• Middle Aged
• Neuropsychological Tests
• Plasma (virology)
• Viral Load
• Young Adult