Office of Research and Development, Taipei Medical University, Taipei, Taiwan.
Yuli Veterans Hospital, Yuli Township, Hualian County, Taiwan.
Psychiatry Investig. 2014 Apr;11(2):179-85. doi: 10.4306/pi.2014.11.2.179. Epub 2014 Apr 11.
Metabolic abnormalities, e.g., diabetes, are common among schizophrenia patients. Peroxisome proliferator activated receptor-γ (PPAR-γ) regulates glucose/lipid metabolisms, and schizophrenia like syndrome may be induced by actions involving retinoid X receptor-α/PPAR-γ heterodimers. We examined a possible role of the PPAR-γ gene in metabolic traits and psychosis profile in schizophrenia patients exposed to antipsychotics.
Single nucleotide polymorphisms (SNPs) of the PPAR-γ gene and a serial of metabolic traits were determined in 394 schizophrenia patients, among which 372 were rated with Positive and Negative Syndrome Scale (PANSS).
SNP-10, -12, -18, -19, -20 and -26 were associated with glycated hemoglobin (HbA1c) whereas SNP-18, -19, -20 and -26 were associated with fasting plasma glucose (FPG). While SNP-23 was associated with triglycerides, no associations were identified between the other SNPs and lipids. Further haplotype analysis demonstrated an association between the PPAR-γ gene and psychosis profile.
Our study suggests a role of the PPAR-γ gene in altered glucose levels and psychosis profile in schizophrenia patients exposed to antipsychotics. Although the Pro12Ala at exon B has been concerned an essential variant in the development of obesity, the lack of association of the variant with metabolic traits in this study should not be treated as impossibility or a proof of error because other factors, e.g., genes regulated by PPAR-γ, may have complicated the development of metabolic abnormalities. Whether the PPAR-γ gene modifies the risk of metabolic abnormalities or psychosis, or causes metabolic abnormalities that lead to psychosis, remains to be examined.
代谢异常，如糖尿病，在精神分裂症患者中很常见。过氧化物酶体增殖物激活受体-γ（PPAR-γ）调节葡萄糖/脂质代谢，视黄酸 X 受体-α/PPAR-γ 异二聚体的作用可能会引起类似精神分裂症的综合征。我们研究了 PPAR-γ 基因在接受抗精神病药物治疗的精神分裂症患者的代谢特征和精神病特征中的可能作用。
在 394 名精神分裂症患者中测定了 PPAR-γ 基因的单核苷酸多态性（SNP）和一系列代谢特征，其中 372 名患者接受了阳性和阴性综合征量表（PANSS）评分。
SNP-10、-12、-18、-19、-20 和 -26 与糖化血红蛋白（HbA1c）相关，而 SNP-18、-19、-20 和 -26 与空腹血糖（FPG）相关。SNP-23 与甘油三酯相关，而其他 SNP 与脂质没有相关性。进一步的单体型分析表明，PPAR-γ 基因与精神病特征有关。
我们的研究表明，PPAR-γ 基因在接受抗精神病药物治疗的精神分裂症患者的血糖水平和精神病特征改变中起作用。虽然外显子 B 的 Pro12Ala 被认为是肥胖发生的重要变异，但该变异与本研究中代谢特征的缺乏相关性不应被视为不可能或错误的证据，因为其他因素，如受 PPAR-γ 调节的基因，可能会使代谢异常的发展变得复杂。PPAR-γ 基因是否改变代谢异常或精神病的风险，或导致导致精神病的代谢异常，仍有待进一步研究。
