Department of Forensic Psychiatry, School of Medicine & Forensics, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi, 710061, China; Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine & Forensics, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi, 710061, China.
Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi, 710061, China.
Schizophr Res. 2020 Jan;215:250-255. doi: 10.1016/j.schres.2019.09.015. Epub 2019 Oct 22.
The SNAP25 gene is involved in the development of antipsychotic-induced weight gain (AIWG) or metabolic syndrome during antipsychotics use in Americans and Europeans, but its role in Asians remains unknown. To identify common variants in SNAP25 associated with schizophrenia and evaluate their effects on AIWG and antipsychotic responses in Han Chinese individuals with schizophrenia, we conducted a two-stage case-control study of 3,243 patients and 6,154 healthy controls. 2128 inpatients in the replication stage have received conventional treatment with an antipsychotic monotherapy (Haloperidol, Olanzapine or Risperidone) for 10 weeks at least. Weight change, antipsychotic responses and metabolic indices change were assessed during treatments. Three SNPs were significantly associated with schizophrenia in samples (rs6039769, P = 6.64 × 10; rs3787283, P = 0.004283; rs3746544, P = 2.51 × 10). Of these, rs6039769 is a novel schizophrenia-associated SNP and is uncorrelated with the other two variants, which have previously been associated with schizophrenia in European-ancestry samples. Rs6039769 was significantly associated with AIWG (P < 0.001), but not with antipsychotic responses or metabolic indices. Another two SNPs were not associated with AIWG or antipsychotic responses or metabolic indices. Overall, there were significant differences in antipsychotic responses and metabolic indices among the three treatment groups. Our findings suggest that SNAP25 gene may contribute to the susceptibility of AIWG and even metabolic disturbances. A prior identification of high-risk of patients with rs6039769 would contribute to a better precision of the pharmacological treatment.
SNAP25 基因参与了抗精神病药诱导的体重增加（AIWG）或代谢综合征的发生，这在使用抗精神病药物的美国人和欧洲人中已有研究报道，但在亚洲人中的作用尚不清楚。为了确定与精神分裂症相关的 SNAP25 常见变异，并评估其对中国汉族精神分裂症患者 AIWG 和抗精神病药物反应的影响，我们进行了一项两阶段的病例对照研究，纳入了 3243 例患者和 6154 例健康对照者。在验证阶段，2128 例住院患者接受了常规治疗，使用单一抗精神病药物（氟哌啶醇、奥氮平或利培酮）治疗至少 10 周。在治疗期间评估体重变化、抗精神病药物反应和代谢指标变化。在样本中，有 3 个 SNP 与精神分裂症显著相关（rs6039769，P=6.64×10；rs3787283，P=0.004283；rs3746544，P=2.51×10）。其中，rs6039769 是一个新的与精神分裂症相关的 SNP，与另外两个变异没有相关性，而这两个变异之前已被报道与欧洲血统样本中的精神分裂症相关。rs6039769 与 AIWG 显著相关（P<0.001），但与抗精神病药物反应或代谢指标无关。另外两个 SNP 与 AIWG 或抗精神病药物反应或代谢指标无关。总体而言，三个治疗组之间的抗精神病药物反应和代谢指标存在显著差异。我们的研究结果表明，SNAP25 基因可能与 AIWG 甚至代谢紊乱的易感性有关。在 rs6039769 患者中提前识别出高风险，有助于更好地进行药物治疗的精准化。
