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

April D. Thames, Marisa S. Briones, Larry I. Magpantay, Otoniel Martinez-Maza, Elyse J. Singer, Charles H. Hinkin, Susan Morgello, Benjamin Gelman, David J. Moore, Keith Heizerling, Andrew J. Levine

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 HIVinfected 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-a), interferon-gamma (IFN-g), soluble tumor necrosis factor receptor 2, sIL-6Ra, 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.

Original languageEnglish (US)
Pages (from-to)1483-1491
Number of pages9
JournalAIDS
Volume29
Issue number12
DOIs
StatePublished - Jul 31 2015

Fingerprint

Chemokine CCL2
Cerebrospinal Fluid
Genotype
HIV
Ligands
Viral Load
Alleles
B-Cell Activating Factor
Receptors, Tumor Necrosis Factor, Type II
Neuropsychological Tests
CD4 Lymphocyte Count
Interferon-alpha
Cognition
Interferon-gamma
Interleukin-2
Single Nucleotide Polymorphism
Interleukin-6
Blood Cells
Tumor Necrosis Factor-alpha
Cross-Sectional Studies

Keywords

  • CCL2
  • HIV-associated neurocognitive disorder
  • HIV/AIDS
  • MCP-1
  • plasma viral load
  • rs1024611

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Thames, A. D., Briones, M. S., Magpantay, L. I., Martinez-Maza, O., Singer, E. J., Hinkin, C. H., ... Levine, A. J. (2015). 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. AIDS, 29(12), 1483-1491. https://doi.org/10.1097/QAD.0000000000000706

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. / Thames, April D.; Briones, Marisa S.; Magpantay, Larry I.; Martinez-Maza, Otoniel; Singer, Elyse J.; Hinkin, Charles H.; Morgello, Susan; Gelman, Benjamin; Moore, David J.; Heizerling, Keith; Levine, Andrew J.

In: AIDS, Vol. 29, No. 12, 31.07.2015, p. 1483-1491.

Research output: Contribution to journalArticle

Thames, AD, Briones, MS, Magpantay, LI, Martinez-Maza, O, Singer, EJ, Hinkin, CH, Morgello, S, Gelman, B, Moore, DJ, Heizerling, K & Levine, AJ 2015, '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', AIDS, vol. 29, no. 12, pp. 1483-1491. https://doi.org/10.1097/QAD.0000000000000706
Thames, April D. ; Briones, Marisa S. ; Magpantay, Larry I. ; Martinez-Maza, Otoniel ; Singer, Elyse J. ; Hinkin, Charles H. ; Morgello, Susan ; Gelman, Benjamin ; Moore, David J. ; Heizerling, Keith ; Levine, Andrew J. / 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. In: AIDS. 2015 ; Vol. 29, No. 12. pp. 1483-1491.
@article{c42b9d6c44f5420ab28b15285a49f5cb,
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",
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 HIVinfected 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-a), interferon-gamma (IFN-g), soluble tumor necrosis factor receptor 2, sIL-6Ra, 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.",
keywords = "CCL2, HIV-associated neurocognitive disorder, HIV/AIDS, MCP-1, plasma viral load, rs1024611",
author = "Thames, {April D.} and Briones, {Marisa S.} and Magpantay, {Larry I.} and Otoniel Martinez-Maza and Singer, {Elyse J.} and Hinkin, {Charles H.} and Susan Morgello and Benjamin Gelman and Moore, {David J.} and Keith Heizerling and Levine, {Andrew J.}",
year = "2015",
month = "7",
day = "31",
doi = "10.1097/QAD.0000000000000706",
language = "English (US)",
volume = "29",
pages = "1483--1491",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - 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

AU - Thames, April D.

AU - Briones, Marisa S.

AU - Magpantay, Larry I.

AU - Martinez-Maza, Otoniel

AU - Singer, Elyse J.

AU - Hinkin, Charles H.

AU - Morgello, Susan

AU - Gelman, Benjamin

AU - Moore, David J.

AU - Heizerling, Keith

AU - Levine, Andrew J.

PY - 2015/7/31

Y1 - 2015/7/31

N2 - 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 HIVinfected 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-a), interferon-gamma (IFN-g), soluble tumor necrosis factor receptor 2, sIL-6Ra, 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.

AB - 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 HIVinfected 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-a), interferon-gamma (IFN-g), soluble tumor necrosis factor receptor 2, sIL-6Ra, 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.

KW - CCL2

KW - HIV-associated neurocognitive disorder

KW - HIV/AIDS

KW - MCP-1

KW - plasma viral load

KW - rs1024611

UR - http://www.scopus.com/inward/record.url?scp=84942601769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942601769&partnerID=8YFLogxK

U2 - 10.1097/QAD.0000000000000706

DO - 10.1097/QAD.0000000000000706

M3 - Article

C2 - 26244388

AN - SCOPUS:84942601769

VL - 29

SP - 1483

EP - 1491

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 12

ER -