Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.

The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific CHRFAM7A gene and its 2bp deletion polymorphism (Δ2bp variant) encodes a structurally-deficient α7nAChRs that may impact the anti-inflammatory function. We studied 45 spinal...

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Autores principales: Mingkuan Lin, Wan Huang, Nadine Kabbani, Mark M Theiss, John F Hamilton, James M Ecklund, Yvette P Conley, Yoram Vodovotz, David Brienza, Amy K Wagner, Emily Robbins, Gwendolyn A Sowa, Robert H Lipsky
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:4a386b81cf444528804f9e1a7194413f2021-11-25T05:54:17ZEffect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.1932-620310.1371/journal.pone.0251110https://doaj.org/article/4a386b81cf444528804f9e1a7194413f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251110https://doaj.org/toc/1932-6203The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific CHRFAM7A gene and its 2bp deletion polymorphism (Δ2bp variant) encodes a structurally-deficient α7nAChRs that may impact the anti-inflammatory function. We studied 45 spinal cord injury (SCI) patients for up to six weeks post SCI to investigate the role of the Δ2bp variant on multiple circulating inflammatory mediators and two outcome measures (neuropathic pain and risk of pressure ulcers). The patient's SCI were classified as either severe or mild. Missing values were imputed. Overall genetic effect was conducted with independent sample t-test and corrected with false discovery rate (FDR). Univariate analysis and regression analysis were applied to evaluate the Δ2bp effects on temporal variation of inflammatory mediators post SCI and their interaction with outcome measures. In severe SCI, the Δ2bp carriers showed higher levels of circulating inflammatory mediators than the Δ2bp non-carriers in TNF-α (FDR = 9.6x10-4), IFN-γ (FDR = 1.3x10-3), IL-13 (FDR = 1.6x10-3), CCL11 (FDR = 2.1x10-3), IL-12p70 (FDR = 2.2x10-3), IL-8 (FDR = 2.2x10-3), CXCL10 (FDR = 3.1x10-3), CCL4 (FDR = 5.7x10-3), IL-12p40 (FDR = 7.1x10-3), IL-1b (FDR = 0.014), IL-15 (FDR = 0.024), and IL-2 (FDR = 0.037). IL-8 and CCL2 were negatively associated with days post injury (DPI) for the Δ2bp carriers (P = 2x10-7 and P = 2x10-8, respectively) and IL-5 was positively associated with DPI for the Δ2bp non-carriers (P = 0.015). Neuropathic pain was marginally positively associated with IL-13 for the Δ2bp carriers (P = 0.056). In mild SCI, the Δ2bp carriers had lower circulating levels of IL-15 (FDR = 0.04) than the Δ2bp non-carriers. Temporal variation of inflammatory mediators post SCI was not associated with the Δ2bp variant. For the mild SCI Δ2bp carriers, risk of pressure ulcers was positively associated with circulating levels of IFN-γ, CXCL10, and CCL4 and negatively associated with circulating levels of IL-12p70. These findings support an important role for the human-specific CHRFAM7A Δ2bp gene variant in modifying anti-inflammatory function of α7nAChRs following SCI.Mingkuan LinWan HuangNadine KabbaniMark M TheissJohn F HamiltonJames M EcklundYvette P ConleyYoram VodovotzDavid BrienzaAmy K WagnerEmily RobbinsGwendolyn A SowaRobert H LipskyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251110 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mingkuan Lin
Wan Huang
Nadine Kabbani
Mark M Theiss
John F Hamilton
James M Ecklund
Yvette P Conley
Yoram Vodovotz
David Brienza
Amy K Wagner
Emily Robbins
Gwendolyn A Sowa
Robert H Lipsky
Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.
description The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific CHRFAM7A gene and its 2bp deletion polymorphism (Δ2bp variant) encodes a structurally-deficient α7nAChRs that may impact the anti-inflammatory function. We studied 45 spinal cord injury (SCI) patients for up to six weeks post SCI to investigate the role of the Δ2bp variant on multiple circulating inflammatory mediators and two outcome measures (neuropathic pain and risk of pressure ulcers). The patient's SCI were classified as either severe or mild. Missing values were imputed. Overall genetic effect was conducted with independent sample t-test and corrected with false discovery rate (FDR). Univariate analysis and regression analysis were applied to evaluate the Δ2bp effects on temporal variation of inflammatory mediators post SCI and their interaction with outcome measures. In severe SCI, the Δ2bp carriers showed higher levels of circulating inflammatory mediators than the Δ2bp non-carriers in TNF-α (FDR = 9.6x10-4), IFN-γ (FDR = 1.3x10-3), IL-13 (FDR = 1.6x10-3), CCL11 (FDR = 2.1x10-3), IL-12p70 (FDR = 2.2x10-3), IL-8 (FDR = 2.2x10-3), CXCL10 (FDR = 3.1x10-3), CCL4 (FDR = 5.7x10-3), IL-12p40 (FDR = 7.1x10-3), IL-1b (FDR = 0.014), IL-15 (FDR = 0.024), and IL-2 (FDR = 0.037). IL-8 and CCL2 were negatively associated with days post injury (DPI) for the Δ2bp carriers (P = 2x10-7 and P = 2x10-8, respectively) and IL-5 was positively associated with DPI for the Δ2bp non-carriers (P = 0.015). Neuropathic pain was marginally positively associated with IL-13 for the Δ2bp carriers (P = 0.056). In mild SCI, the Δ2bp carriers had lower circulating levels of IL-15 (FDR = 0.04) than the Δ2bp non-carriers. Temporal variation of inflammatory mediators post SCI was not associated with the Δ2bp variant. For the mild SCI Δ2bp carriers, risk of pressure ulcers was positively associated with circulating levels of IFN-γ, CXCL10, and CCL4 and negatively associated with circulating levels of IL-12p70. These findings support an important role for the human-specific CHRFAM7A Δ2bp gene variant in modifying anti-inflammatory function of α7nAChRs following SCI.
format article
author Mingkuan Lin
Wan Huang
Nadine Kabbani
Mark M Theiss
John F Hamilton
James M Ecklund
Yvette P Conley
Yoram Vodovotz
David Brienza
Amy K Wagner
Emily Robbins
Gwendolyn A Sowa
Robert H Lipsky
author_facet Mingkuan Lin
Wan Huang
Nadine Kabbani
Mark M Theiss
John F Hamilton
James M Ecklund
Yvette P Conley
Yoram Vodovotz
David Brienza
Amy K Wagner
Emily Robbins
Gwendolyn A Sowa
Robert H Lipsky
author_sort Mingkuan Lin
title Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.
title_short Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.
title_full Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.
title_fullStr Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.
title_full_unstemmed Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.
title_sort effect of chrfam7a δ2bp gene variant on secondary inflammation after spinal cord injury.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/4a386b81cf444528804f9e1a7194413f
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