精神分裂症患者使用非典型抗精神病药物治疗时，SCAP与SREBF1基因多态性与代谢综合征之间的关联。
Association between SCAP and SREBF1 gene polymorphisms and metabolic syndrome in schizophrenia patients treated with atypical antipsychotics.
作者信息
Yang Lin, Chen Jianhua, Li Yan, Wang Yan, Liang Shiqiao, Shi Yongyong, Shi Shenxun, Xu Yifeng
机构信息
a Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center , Shanghai Jiao Tong University School of Medicine , Shanghai , 200030 , China ;
b Department of Psychiatry , Huashan Hospital, Fudan University , Shanghai , 200021 , China ;
出版信息
World J Biol Psychiatry. 2016 Sep;17(6):467-74. doi: 10.3109/15622975.2016.1165865. Epub 2016 Apr 28.
OBJECTIVES
The use of atypical antipsychotics (AAPs) in the treatment of schizophrenia has been relevant because of the high prevalence of metabolic syndrome (MetS). The sterol-regulatory element-binding protein (SREBP) pathway may contribute to the underlying pathophysiology of AAP-induced metabolic adverse effects. We explored the association between the variants of the sterol-regulatory element-binding transcription factor-1 (SREBF1) gene and the SREBP cleavage-activation protein (SCAP) gene with AAP-induced MetS in a genetic case-control study.
METHODS
Eleven single nucleotide polymorphisms (SNPs) of SREBF1 and five of SCAP were genotyped in a Han Chinese population in Beijing, China: a sample of 722 schizophrenia patients on monotherapy with AAPs (clozapine, olanzapine or risperidone). Metabolic parameters were collected and evaluated for MetS criteria.
RESULTS
The rs11654081 T-allele of the SREBF1 gene was significantly associated with an increased risk for MetS after correction (P = 0.019, odds ratio, OR =2.56, 95% confidence interval, CI: 1.4 4-4.54). The rs11654081-TT genotype appeared more frequently in MetS than in non-MetS after correction (P = 0.026, OR =2.37, 95% CI: 1.3 6-4.12). SCAP polymorphisms with drug-induced MetS were negative in this study.
CONCLUSIONS
The genetic polymorphisms of SREBF1 could play a role in the mechanism for interindividual variation of AAP-induced MetS.
目的
由于代谢综合征（MetS）的高患病率，非典型抗精神病药物（AAPs）在精神分裂症治疗中的应用备受关注。固醇调节元件结合蛋白（SREBP）途径可能在AAPs诱导的代谢不良反应的潜在病理生理学中起作用。我们在一项基因病例对照研究中探讨了固醇调节元件结合转录因子1（SREBF1）基因和SREBP裂解激活蛋白（SCAP）基因的变异与AAPs诱导的MetS之间的关联。
方法
在中国北京的汉族人群中，对SREBF1的11个单核苷酸多态性（SNPs）和SCAP的5个单核苷酸多态性进行基因分型：722例接受AAPs（氯氮平、奥氮平或利培酮）单一疗法的精神分裂症患者样本。收集代谢参数并根据MetS标准进行评估。
结果
校正后，SREBF1基因的rs11654081 T等位基因与MetS风险增加显著相关（P = 0.019，优势比，OR = 2.56，95%置信区间，CI：1.44 - 4.54）。校正后，rs11654081 - TT基因型在MetS患者中出现的频率高于非MetS患者（P = 0.026，OR = 2.37，95% CI：1.36 - 4.12）。本研究中SCAP多态性与药物诱导的MetS呈阴性相关。
结论
SREBF1的基因多态性可能在AAPs诱导的MetS个体间差异机制中起作用。
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