Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results.
Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results.
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脑源性神经营养因子基因 Val66Met 多态性与氯氮平诱导的代谢综合征的关联研究：初步结果
DOI：
10.1371/journal.pone.0072652
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Zhang Y;Chen M;Wu Z;Chen J;Yu S;Fang Y;Zhang C
在接受非典型抗精神病药（AAP）治疗的患者中，代谢综合征（MetS）的患病率较高，即使在AAP中，氯氮平治疗也显示与MetS的长期发生率较高相关。同样，脑源性神经营养因子（BDNF）缺乏也被报道会导致代谢特征，如摄食量增加、食欲过旺和肥胖等。BDNF基因中的Val 66 Met可能以性别特异性方式赋予对氯氮平诱导的MetS的易感性，因为在我们以前的研究中观察到Val 66 Met多态性与性别之间的相互作用。根据国家胆固醇教育计划成人治疗小组III的诊断标准，将199例接受氯氮平治疗的精神分裂症患者分为两组，MetS和非MetS。检测Val 66 Met基因多态性，并检测空腹血糖（GLU）、甘油三酯（TG）和高密度脂蛋白胆固醇（HDL）水平。有一种趋势表明纯合Met/Met基因型与男性患者的MetS之间存在显著相关性（OR = 2.39; 95% CI：1.05-5.41; p = 0.039;校正p = 0.078）。 在ATPIII标准中列出的六个风险因素中，我们发现男性空腹血糖水平与Val 66 Met多态性之间存在显著相关性（p = 0.005;校正p = 0.03），但在女性中没有相关性（p = 0.65）。 对男性的事后分析显示，Met/Met携带者的空腹血糖水平显著高于瓦尔/瓦尔或瓦尔/Met基因型携带者（分别为p= 0.007;校正p = 0.042和p = 0.002;校正p =0.012）。 总之，我们观察到Val 66 Met多态性和氯氮平诱导的MetS之间的性别特异性的方式弱关联。虽然是初步的，但这些发现促使进一步的大规模纵向研究来复制这些发现。
The prevalence of the metabolic syndrome (MetS) is higher among patients receiving atypical antipsychotics (AAPs) treatment, and even among AAPs, treatment with clozapine has been shown to be associated with a higher long-term incidence rate of MetS. Likewise, brain-derived neurotrophic factor (BDNF) deficiency has been reported to result in metabolic traits, such as increased food intake, hyperphagia and obesity, etc. In this study, we hypothesized that a functional polymorphism (Val66Met) in the BDNF gene may confer susceptibility to clozapine-induced MetS, potentially in a sex-specific manner, since an interaction between Val66Met polymorphism and sex was observed in our previous studies. A total of 199 schizophrenia patients being treated with clozapine were divided into two groups, MetS and non-MetS, based on the diagnostic criteria of the National Cholesterol Education Program's Adult Treatment Panel III. We genotyped the Val66Met polymorphism, and measured the serum levels of fasting glucose (GLU), triglyceride (TG) and high density lipoprotein cholesterol (HDL). There was a trend indicating a significant association between the homozygous Met/Met genotype and MetS in male patients (OR = 2.39; 95% CI: 1.05–5.41; p = 0.039; corrected p = 0.078). Among the six risk factors listed in the ATPIII criteria, we found a significant association between fasting GLU levels and Val66Met polymorphism in males (p = 0.005; corrected p = 0.03), but not in females (p = 0.65). Post-hoc analysis in males revealed that the Met/Met carriers had significant higher levels of fasting GLU than those with Val/Val or Val/Met genotypes (p = 0.007; corrected p = 0.042 and p = 0.002; corrected p = 0.012, respectively). In conclusion, we observed a weak association between the Val66Met polymorphism and clozapine-induced MetS in a sex-specific manner. While preliminary, such findings prompt further, large-scale longitudinal studies to replicate these findings.
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