Khasanova Aiperi K, Sosin Dmitriy N, Mosolov Sergey N, Mirzaev Karin B, Sychev Dmitriy A
Russian Medical Academy of Continuous Professional Education, 2/1, Bldg. 1, Barrikadnaya St., Moscow 125993, Russia.
Moscow Research Institute of Psychiatry, Branch of the Serbsky National Medical Research Centre for Psychiatry and Narcology, 3, Poteshnaia St., Moscow 107076, Russia.
J Clin Med. 2025 May 30;14(11):3861. doi: 10.3390/jcm14113861.
Clozapine, the gold-standard treatment for treatment-resistant schizophrenia, is linked to metabolic disturbances such as weight gain and metabolic syndrome (MetS). This systematic review and meta-analysis evaluated the association between polymorphisms and these adverse effects. Following PRISMA guidelines, 27 studies (n = 4044 patients, including 1804 clozapine-treated) were analyzed. A meta-analysis revealed that the rs3813929 T allele was associated with a smaller increase in body weight, showing a mean BMI difference of 0.59 kg/m (95% CI: -1.02 to -0.17; ** = 0.006), particularly in males. The rs1414334 C allele doubled MetS risk (OR: 2.15; 95% CI: 1.42-3.27; ** = 0.0003). Haplotype analyses suggested combined genetic effects, though findings for other polymorphisms were inconsistent. Key limitations include study heterogeneity, small sample sizes, and the predominance of mixed antipsychotic regimens (clozapine with other psychotropics) in included studies, potentially confounding metabolic outcomes. Despite this, rs3813929 and rs1414334 emerge as promising pharmacogenetic markers for predicting metabolic risks. These results highlight the need for large-scale, prospective studies across diverse populations to validate associations and optimize personalized monitoring strategies. Implementing genetic screening could enhance early intervention, improving long-term outcomes for clozapine-treated patients.
氯氮平是难治性精神分裂症的金标准治疗药物，与体重增加和代谢综合征（MetS）等代谢紊乱有关。本系统评价和荟萃分析评估了基因多态性与这些不良反应之间的关联。按照PRISMA指南，对27项研究（n = 4044例患者，其中1804例接受氯氮平治疗）进行了分析。荟萃分析显示，rs3813929的T等位基因与体重增加幅度较小有关，平均体重指数差异为0.59 kg/m²（95%CI：-1.02至-0.17；P = 0.006），在男性中尤为明显。rs1414334的C等位基因使代谢综合征风险增加一倍（OR：2.15；95%CI：1.42 - 3.27；P = 0.0003）。单倍型分析提示存在联合遗传效应，不过其他多态性的研究结果并不一致。主要局限性包括研究的异质性、样本量小以及纳入研究中联合抗精神病药物治疗方案（氯氮平与其他精神药物联用）占主导地位，这可能混淆代谢结果。尽管如此，rs3813929和rs1414334有望成为预测代谢风险的药物遗传学标志物。这些结果凸显了开展大规模、跨不同人群的前瞻性研究以验证关联并优化个性化监测策略的必要性。实施基因筛查可加强早期干预，改善氯氮平治疗患者的长期预后。
