Zhang Qian, Wan Yajie, Du Xinzhe, Gao Yao, Wang Xiao, Wu Kewen, Zheng Xiaohu, Wang Yu, Zhao Cheng, Li Li, Guo Xianju, Li Xinrong, Liu Sha, Xu Yong
Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China.
Front Psychiatry. 2022 Oct 21;13:1014952. doi: 10.3389/fpsyt.2022.1014952. eCollection 2022.
The pathogenesis of schizophrenia is associated with neuropeptide Y (NPY) gene polymorphism to explore the relationship between rs16141, rs16145, and rs5573 polymorphisms in the NPY gene and antipsychotics response in the Chinese population.
The unrelated 228 Chinese Han patients with schizophrenia were enrolled in the present study. Genotypisation within NPY gene was performed using the KASP genotyping assays. Before treatment and on the weekends of the 2nd, 4th, and 8th weeks after treatment, the medication status of the patients was recorded and the positive and negative syndrome scale (PANSS) was used to evaluate the clinical effect. A reduction in total PANSS scores ≥50% were classified as good responders, while others were poor responders. We evaluated the association between NPY gene and antipsychotic efficacy by comparing allele and genotype distribution, correlation analysis, linkage imbalance, and five genetic models between the two groups.
No significant associations were found in the rs16141, rs16145, and rs5573 of NPY and antipsychotic treatment response (all > 0.05). There was no significant relationship between the three SNPs polymorphisms in the NPY gene and the changes of positive, negative and general psychopathology subscales scores at each stage (all > 0.05). The distribution of genotype and allele frequencies of locus rs16141 was not statistically difference between good responders and poor responders (genotype: χ2 =4.088, =0.043, = 0.129; allele: χ = 4.088, = 0.027, = 0.081). The allele distribution of rs5573 was significantly different between groups, yet the difference was disappeared after correcting (χ = 4.136, = 0.042, =0.126). The distribution frequencies of TA/TG and GG haplotypes constituted by rs16141 and rs5573 showed no statistical difference between the two groups ( > 0.05). In recessive inheritance mode, NPYrs5573 was found to be associated with antipsychotic drug response (G/G vs. A/A +A/G: = 0.028, AIC = 197.2, BIC = 210.9).
This study didn't found association between polymorphisms in the NPY gene locus (rs16141, rs16145, and rs5573) and the response to antipsychotics after Bonferroni correction. The polymorphism of NPY gene and the efficacy of antipsychotic drugs in patients with schizophrenia need further study.
精神分裂症的发病机制与神经肽Y(NPY)基因多态性有关,旨在探讨中国人群中NPY基因rs16141、rs16145和rs5573多态性与抗精神病药物反应之间的关系。
本研究纳入了228名无亲缘关系的中国汉族精神分裂症患者。采用KASP基因分型检测法对NPY基因进行基因分型。在治疗前以及治疗后第2、4和8周的周末,记录患者的用药情况,并使用阳性和阴性症状量表(PANSS)评估临床疗效。PANSS总分降低≥50%被归类为良好反应者,其他为不良反应者。我们通过比较两组之间的等位基因和基因型分布、相关性分析、连锁不平衡和五种遗传模型,评估NPY基因与抗精神病药物疗效之间的关联。
在NPY的rs16141、rs16145和rs5573与抗精神病药物治疗反应之间未发现显著关联(均>0.05)。NPY基因中的三个单核苷酸多态性与各阶段阳性、阴性和一般精神病理学亚量表评分的变化之间无显著关系(均>0.05)。rs16141位点的基因型和等位基因频率在良好反应者和不良反应者之间的分布无统计学差异(基因型:χ2 =4.088,P =0.043,df = 0.129;等位基因:χ = 4.088,P = 0.027,df = 0.081)。rs5573的等位基因分布在两组之间存在显著差异,但校正后差异消失(χ = 4.136,P = 0.042,df=0.126)。由rs16141和rs5573构成的TA/TG和GG单倍型的分布频率在两组之间无统计学差异(>0.05)。在隐性遗传模式下,发现NPYrs5573与抗精神病药物反应相关(G/G vs. A/A +A/G:P = 0.028,AIC = 197.2,BIC = 210.9)。
本研究在Bonferroni校正后未发现NPY基因位点(rs16141、rs16145和rs5573)的多态性与抗精神病药物反应之间存在关联。NPY基因多态性与精神分裂症患者抗精神病药物疗效之间的关系有待进一步研究。