Schizophrenia is a severe highly heritable mental disorder. The clinical heterogeneity of schizophrenia is expressed in the difference in the leading symptoms and course of the disease. Identifying the genetic variants that affect clinical heterogeneity may ultimately reveal the genetic basis of the features of schizophrenia and suggest novel treatment targets. PIP5K2A (Phosphatidylinositol-4-Phosphate 5-Kinase Type II Alpha) has been investigated as a potential susceptibility gene for schizophrenia. In this work, we studied the possible association between eleven polymorphic variants of PIP5K2A and the clinical features of schizophrenia in a population of 384 white Siberian patients with schizophrenia. Genotyping was carried out on QuantStudio 5 Real-Time PCR System with a TaqMan Validate SNP Genotyping Assay (Applied Biosystems, USA). PIP5K2A rs8341 (χ2 = 6.559, p = 0.038) and rs946961 (χ2 = 5.976, p = 0.049) showed significant association with course of schizophrenia (continuous or episodic). The rs8341*CT (OR = 1.63, 95% CI: 1.04–2.54) and rs946961*CC (OR = 5.17, 95% CI: 1.20–22.21) genotypes were associated with a continuous type of course, while the rs8341*TT genotype (OR = 0.53, 95% CI: 0.29–0.97) was associated with an episodic type of course of schizophrenia. Therefore rs8341*TT genotype presumably has protective effect against the more severe continuous course of schizophrenia compared to the episodic one. Our experimental data confirm that PIP5K2A is a genetic factor influencing the type of course of schizophrenia in Siberian population. Disturbances in the phosphatidylinositol pathways may be a possible reason for the transition to a more severe continuous course of schizophrenia.

中文翻译：

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PIP5K2A的遗传多态性与精神分裂症的病程

精神分裂症是一种严重的高度遗传性精神障碍。精神分裂症的临床异质性以疾病的主要症状和病程的差异表示。确定影响临床异质性的遗传变异可能最终揭示精神分裂症特征的遗传基础，并提出新的治疗靶标。已经研究了PIP5K2A（磷脂酰肌醇-4-磷酸5-激酶II型α）作为精神分裂症的潜在易感基因。在这项工作中，我们研究了384名西伯利亚白人精神分裂症患者中PIP5K2A的11个多态性变异与精神分裂症临床特征之间的可能联系。基因分型是在QuantStudio 5实时PCR系统上使用TaqMan验证SNP基因分型分析（美国应用生物系统公司）进行的。PIP5K2A rs8341（χ2= 6.559，p = 0.038）和rs946961（χ2= 5.976，p = 0.049）与精神分裂症的病程密切相关（连续或发作）。rs8341 * CT（OR = 1.63，95％CI：1.04–2.54）和rs946961 * CC（OR = 5.17，95％CI：1.20–22.21）基因型与连续型相关，而rs8341 * TT基因型（OR = 0.53，95％CI：0.29–0.97）与精神分裂症的发作过程类型有关。因此，与偶发性发作相比，rs8341 * TT基因型可能对更严重的精神分裂症持续病程具有保护作用。我们的实验数据证实，PIP5K2A是影响西伯利亚人群精神分裂症病程类型的遗传因素。