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

Autor: Mark M. Theiss, Nadine Kabbani, Gwendolyn Sowa, Robert H. Lipsky, Yoram Vodovotz, David M. Brienza, Wan Huang, Mingkuan Lin, John F. Hamilton, James M. Ecklund, Emily Robbins, Amy K. Wagner, Yvette P. Conley
Rok vydání: 2020
Předmět:
Male
Critical Care and Emergency Medicine
alpha7 Nicotinic Acetylcholine Receptor
Physiology
Gastroenterology
Nervous System
Injury Severity Score
Polymorphism (computer science)
Immune Physiology
Medicine and Health Sciences
Spinal Cord Injury
Spinal cord injury
Immune Response
CCL11
Trauma Medicine
Cerebrospinal Fluid
Ulcers
Univariate analysis
Innate Immune System
Multidisciplinary
Middle Aged
Myelitis
Body Fluids
Neurology
Neuropathic pain
Medicine
Cytokines
Female
medicine.symptom
Anatomy
Traumatic Injury
Research Article
Adult
medicine.medical_specialty
Adolescent
Science
Immunology
Pain
Inflammation
CCL4
CCL2
Young Adult
Signs and Symptoms
Internal medicine
medicine
Genetics
Humans
Spinal Cord Injuries
Aged
Neuropathic Pain
business.industry
Genetic Variation
Biology and Life Sciences
Molecular Development
medicine.disease
Immune System
Clinical Medicine
business
Neurotrauma
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 5, p e0251110 (2021)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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