Protective Effect of the MCP-1 Gene Haplotype against Schizophrenia

Abstract

While cytokines and their genetic variants have been intensively studied in schizophrenia, little attention has been focused on chemokines in the last years. The monocyte chemoattractant protein 1 (MCP-1) is known to attract peripheral monocytes to the brain during an inflammatory reaction and to affect the T helper (Th) cell development by stimulating Th2 polarization. Owing to the neuroinflammation in schizophrenia and the variable level of MCP-1 in these patients' sera, we proposed to analyze the impact of functional genetic variants of the MCP-1 gene (MCP-1-2518A/G (rs1024611), MCP-1-362G/C (rs2857656), and MCP-1 int1del554-567 (rs3917887)) in schizophrenic patients. We conducted a case-control study on a Tunisian population composed of 200 patients and 200 controls using RFLP-PCR. Our results indicated that the minor alleles (-2518G and Del554-567) were significantly more prevalent in controls than in patients (P=0.001/adjusted OR = 0.42, P=0.04/adjusted OR = 0.64), whereas, for -362C minor allele, increased risk of schizophrenia was revealed (P=0.001, adjusted OR = 2.38). In conclusion, we have identified the haplotype combination -2581G/-362G/int1del554-567 that could mediate protection against schizophrenia (P=0.0038, OR = 0.19) and the effect could result more strongly from the MCP-1 -2582G with -362G variants, whereas the effect of int1del554-567 may in part be explained by its LD with -362.

Association of VEGF-A and KDR polymorphisms with the development of schizophrenia

“…This predisposition remained valid for the paranoid form and more advanced in the undifferentiated subtype even after adjustment with covariates. This result is similar to that found for MCP-1 -362G/C among the same population 48 . When we compared the severity of disease symptoms, our findings demonstrate also greater symptomatic scores at admission and discharge with statistical significance for the SAPS2 and SANS2 scales according to the dominant genetic model.…”

Inflammation-Mediated Angiogenesis in Ischemic Stroke

“…Both MCP-1 and its receptor C-C chemokine receptor type 2 (CCR2) expressed in the brain are crucial regulators of CNS inflammation and activation of the microglia, involved in various neuroinflammatory diseases (Hinojosa et al, 2011). During inflammatory response, MCP-1 attracts peripheral monocytes to the brain and regulates Th cell development by stimulating Th2 polarization (Saoud et al, 2019). Coincidentally, we have discussed above that the infiltration of Th2 cells to the ischemic hemisphere and the increased Th2-derived cytokine IL-4 can promote angiogenesis during stroke recovery.…”

Friends or foes: The mononuclear phagocyte system in ischemic stroke

“…It is worth noting that there are some signaling cascades between vascular ECs and MPS in the process of angiogenesis ( 61 ). After stroke, ECs secrete a large amount of MCP‐1, which recruits monocyte‐macrophages and regulates the polarization of Th2 cells to secrete IL‐4 ( 68 ). Macrophages polarize towards the M2 phenotype under the influence of IL‐4, and secreted TGF‐β promotes neovascularization ( 69 ).…”