Laboratory of Genetics, Biodiversity and Bioresource Valorization (LR11ES41), Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir, Tunisia.
Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
J Mol Neurosci. 2024 Sep 12;74(3):86. doi: 10.1007/s12031-024-02257-9.
Chemokine ligands and their receptors have acquired less attention than pro- and anti-inflammatory cytokines in schizophrenia (SCZ). Thus, we aimed to examine the impact of functional polymorphisms of the chemokine genes CXCL10, CXCL16, CXCR4, and CCR2 in the development of SCZ. Using PCR-RFLP, we analyzed the selected polymorphisms in a Tunisian cohort composed of 200 patients with SCZ and 200 healthy controls. Our preliminary data suggest that the minor allele A of CXCL10 rs4256246 is significantly associated with likelihood of SCZ (P = 0.00002) and more precisely to paranoid patients with late-onset SCZ (P = 0.0007). However, the mutated allele T of CXCR4 rs2228014 showed a significant protective impact against SCZ (P = 0.000007) and especially to male sex (P = 0.000003). This effect persists among the undifferentiated patients with early-onset SCZ (P = 0.002). Following the stratified analyses, CCR2 rs1799864 and CXCL16 rs2277680 were significantly correlated with the clinical symptoms among disorganized patients. As regards haplotype analysis, we noted that GATG haplotype was associated with protection against SCZ (P = 0.0087) but the AGCG haplotype was correlated with susceptibility to this disease (P = 0.014). Our preliminary results suggested that CXCL10 rs4256246 enhanced susceptibility to SCZ, while CXCR4 rs2228014 seemed to be protective factor. Furthermore, we identified a substantial correlation between CCR2 rs1799864 and CXCL16 rs2277680 with the clinical signs of the disorder. To validate these results and clarify the functional significance of the targeted polymorphisms in SCZ, more independent research is needed.
趋化因子配体及其受体在精神分裂症 (SCZ) 中的研究不如促炎和抗炎细胞因子多。因此，我们旨在研究趋化因子基因 CXCL10、CXCL16、CXCR4 和 CCR2 的功能多态性在 SCZ 发展中的影响。我们使用 PCR-RFLP 分析了一个由 200 名 SCZ 患者和 200 名健康对照组成的突尼斯队列中的选定多态性。我们的初步数据表明，CXCL10 rs4256246 的次要等位基因 A 与 SCZ 的可能性显著相关（P=0.00002），更准确地说是与晚发性 SCZ 的偏执型患者相关（P=0.0007）。然而，CXCR4 rs2228014 的突变等位基因 T 对 SCZ 具有显著的保护作用（P=0.000007），特别是对男性（P=0.000003）。这种效应在早发性 SCZ 的未分化患者中仍然存在（P=0.002）。在分层分析后，CCR2 rs1799864 和 CXCL16 rs2277680 与精神分裂症患者的精神症状显著相关。至于单倍型分析，我们注意到 GATG 单倍型与 SCZ 的保护作用相关（P=0.0087），但 AGCG 单倍型与这种疾病的易感性相关（P=0.014）。我们的初步结果表明，CXCL10 rs4256246 增强了 SCZ 的易感性，而 CXCR4 rs2228014 似乎是保护性因素。此外，我们发现 CCR2 rs1799864 和 CXCL16 rs2277680 与该疾病的临床症状有很大的相关性。为了验证这些结果并阐明靶向多态性在 SCZ 中的功能意义，需要进行更多的独立研究。
