Laboratory of Human Genetics (LR99ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Inserm U955 IMRB, Translational Neuropsychiatry Laboratory and Paris-Est Créteil University, 94010 Créteil, France.
Laboratory of Human Genetics (LR99ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Encephale. 2024 Aug;50(4):380-385. doi: 10.1016/j.encep.2023.08.002. Epub 2023 Sep 23.
Schizophrenia is a complex and chronic neuropsychiatric disorder. Recent genome-wide association studies have identified several at risk genetic variants, including two single nucleotide polymorphisms, namely the rs10503253 and the rs1270942 respectively located in the CSMD1 and the CFB loci. The present case-control study was designed to assess potential associations between the two variants and the risk of developing schizophrenia and disease severity. Further we demonstrate the relationship between these variants and clinical characteristics in a population-group from Tunisia.
In total, 216 patients diagnosed with schizophrenia along with176 healthy controls were included in this case-control study. The molecular analysis of the two polymorphisms was performed using tetra the Primer Amplification Refractory Mutation System-Polymerase Chain method. The statistical analysis was done using Compare V2.1 software, and correlations between genetic results and clinical characteristics were examined by Kruskal-Wallis testing.
The frequency of the rs10503253A allele was found significantly higher among patients with schizophrenia as compared to healthy controls and associated with high negative PANSS scores. While no association was found concerning the implication of the rs1270942 variant in schizophrenia risk, a positive correlation with high positive PANSS scores was further observed.
The present finding confirms the previously reported association between the Cub and Sushi multiple Domain 1 rs10503253A allele and the risk to develop schizophrenia and identified the rs1270942 variant as a potential disease risk modifier. Such observations may be important for the definition of the susceptible immunogenetic background in North African individuals at risk to develop mental disorders.
精神分裂症是一种复杂的慢性神经精神疾病。最近的全基因组关联研究已经确定了几个风险遗传变异，包括两个单核苷酸多态性，分别是 rs10503253 和 rs1270942，分别位于 CSMD1 和 CFB 基因座。本病例对照研究旨在评估这两个变异与精神分裂症发病风险和疾病严重程度之间的潜在关联。此外，我们还在突尼斯人群中展示了这些变体与临床特征之间的关系。
本病例对照研究共纳入 216 例诊断为精神分裂症的患者和 176 例健康对照者。采用四引物扩增受阻突变系统-聚合酶链反应法对两种多态性进行分子分析。使用 Compare V2.1 软件进行统计分析，通过 Kruskal-Wallis 检验检查遗传结果与临床特征之间的相关性。
与健康对照组相比，精神分裂症患者 rs10503253A 等位基因的频率明显升高，且与 PANSS 阴性评分高相关。而 rs1270942 变异对精神分裂症风险的影响则无相关性，但与 PANSS 阳性评分高呈正相关。
本研究结果证实了 Cub 和 Sushi 多结构域 1 rs10503253A 等位基因与精神分裂症发病风险之间的先前报道的关联，并确定 rs1270942 变体为潜在的疾病风险修饰因子。这些观察结果对于确定易患精神障碍的北非个体的易感免疫遗传背景可能很重要。
