Long Jianxiong, Huang Guifeng, Liang Baoyun, Ling Weijun, Guo Xiaojing, Jiang Juan, Su Li
School of Public Health of Guangxi Medical University, Nanning, Guangxi, China.
First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Mol Genet Genomics. 2016 Oct;291(5):1813-21. doi: 10.1007/s00438-016-1221-0. Epub 2016 May 28.
Schizophrenia (SCZ) is a devastating neurodevelopmental disorder. However, the mechanism underlying this highly heritable disorder remains unclear. The dopamine beta-hydroxylase (DBH) gene encodes a key metabolic enzyme of dopamine. Consequently, DBH is considered a candidate gene for SCZ. However, previous studies on its association with SCZ susceptibility have shown conflicting results. Here, we examined association between the rs1611114 polymorphism of DBH and SCZ susceptibility and related clinical symptoms. A total of 691 SCZ patients and 698 age- and gender-matched healthy controls were examined. mRNA expression levels of DBH were measured by quantitative real-time polymerase chain reaction, and the rs1611114 polymorphism was genotyped using the Sequenom MassARRAY platform. Also, the Positive and Negative Syndrome Scale (PANSS) was used to assess SCZ clinical symptoms. Our results show lower DBH mRNA expression levels in SCZ patients than healthy controls (Zhuang: p = 0.000; Han: p = 0.037). Interestingly, the rs1611114 polymorphism was significantly associated with SCZ susceptibility (overdominant model: p = 0.010) in only the Chinese Zhuang population. Furthermore, the rs1611114 polymorphism was associated with PANSS total score (allele T/C: p = 0.015) and general psychopathology score (allele T/C: p = 0.027) in Chinese Zhuang SCZ patients. These results suggest that the DBH gene may play an important role in the occurrence of SCZ. Also, rs1611114 may be associated with SCZ susceptibility and related clinical symptoms in the Chinese Zhuang but not Han Chinese population. Further studies with larger samples of different ethnicities are needed to confirm the role of DBH in SCZ.
精神分裂症(SCZ)是一种具有破坏性的神经发育障碍。然而,这种高度遗传性疾病的潜在机制仍不清楚。多巴胺β-羟化酶(DBH)基因编码多巴胺的一种关键代谢酶。因此,DBH被认为是SCZ的候选基因。然而,先前关于其与SCZ易感性关联的研究结果相互矛盾。在此,我们研究了DBH的rs1611114多态性与SCZ易感性及相关临床症状之间的关联。共检测了691例SCZ患者和698例年龄及性别匹配的健康对照。通过定量实时聚合酶链反应测量DBH的mRNA表达水平,并使用Sequenom MassARRAY平台对rs1611114多态性进行基因分型。此外,使用阳性和阴性症状量表(PANSS)评估SCZ临床症状。我们的结果显示,SCZ患者的DBH mRNA表达水平低于健康对照(壮族:p = 0.000;汉族:p = 0.037)。有趣的是,仅在中国壮族人群中,rs1611114多态性与SCZ易感性显著相关(超显性模型:p = 0.010)。此外,在中国壮族SCZ患者中,rs1611114多态性与PANSS总分(等位基因T/C:p = 0.015)和一般精神病理学评分(等位基因T/C:p = 0.027)相关。这些结果表明,DBH基因可能在SCZ的发生中起重要作用。此外,rs1611114可能与中国壮族而非汉族人群的SCZ易感性及相关临床症状有关。需要对不同种族的更大样本进行进一步研究,以证实DBH在SCZ中的作用。