Begni S, Popoli M, Moraschi S, Bignotti S, Tura G B, Gennarelli M
Genetics Unit, IRCCS 'S Giovanni di Dio', Fatebenefratelli, 25123 Brescia, Italy.
Mol Psychiatry. 2002;7(4):416-8. doi: 10.1038/sj.mp.4000987.
Schizophrenia is a severe psychiatric illness characterised by disturbance of thought, hallucination and delusions.(1) Several studies have suggested that dysfunctions in the glutamatergic transmission are linked to the pathogenesis of schizophrenia, and in particular an excessive activation of glutamate receptors seems to be related to the disruption of neuronal ionic gradients leading to excitotoxicity.(2-7) Numerous findings suggested that the kainate ionotropic glutamate receptors are primarily involved in this mechanism. Recently it has been demonstrated that the GRIK3 gene encoding for the ionotropic glutamate receptor kainate 3 contains a functional polymorphism (T928G) leading to the substitution of a serine with an alanine in position 310 of the protein sequence.(8-11) We performed an association study between the ser310ala GRIK3polymorphism and schizophrenia in a sample of 99 schizophrenic patients and 116 controls. We found a significant difference in the genotype distribution and in particular considering the ala allele as dominant (P = 0.0105, odds ratio (OR) 2.031, 95% confidence interval (CI) 1.177-3.504). This finding suggests a potential role for GRIK3 for susceptibility to schizophrenia.
精神分裂症是一种严重的精神疾病，其特征为思维紊乱、幻觉和妄想。（1）多项研究表明，谷氨酸能传递功能障碍与精神分裂症的发病机制有关，尤其是谷氨酸受体的过度激活似乎与神经元离子梯度的破坏有关，从而导致兴奋性毒性。（2 - 7）大量研究结果表明，海人藻酸离子型谷氨酸受体主要参与这一机制。最近有研究表明，编码离子型谷氨酸受体海人藻酸3的GRIK3基因包含一个功能性多态性（T928G），导致蛋白质序列第310位的丝氨酸被丙氨酸取代。（8 - 11）我们在99例精神分裂症患者和116例对照样本中进行了GRIK3基因ser310ala多态性与精神分裂症的关联研究。我们发现基因型分布存在显著差异，特别是将ala等位基因视为显性时（P = 0.0105，优势比（OR）2.031，95%置信区间（CI）1.177 - 3.504）。这一发现表明GRIK3基因在精神分裂症易感性方面可能发挥作用。
