Tang Siqi, Yao Bin, Li Na, Lin Shuhuang, Huang Zunnan
Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, China.
The Second School of Clinical Medicine, Guangdong Medical University, Dongguan, China.
Cell Physiol Biochem. 2018;51(1):411-428. doi: 10.1159/000495238. Epub 2018 Nov 19.
BACKGROUND/AIMS: The neuropathies Alzheimer's disease (AD), Parkinson's disease (PD), and schizophrenia (SCZ) have different pathological mechanisms but share some common neurodegenerative features, such as gradual loss of neuronal structure and function. Dopamine beta-hydroxylase (DBH), a gene located in the chromosomal region 9q34, plays a crucial role in the process of converting dopamine into norepinephrine (NE). Several case-control studies have reported this pathway in the pathogenesis of AD, PD and SCZ. However, the results are controversial.
We conducted a meta-analysis to estimate the associations between polymorphisms in this gene and AD, PD and SCZ. Seven databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang, SZ Gene and AD Gene) were searched to identify eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations of DBH variants with AD, PD and SCZ susceptibility.
A total of 41 studies involving 10506 cases and 15083 controls were included in our meta-analysis. The analysis results indicated that a lack of association (P > 0.05) was observed between most of the currently available DBH polymorphisms and the neurological diseases AD, PD and SCZ; however, the DBH rs1611131 (allelic model: OR = 0.889, 95% CI: 0.815 - 0.969; dominant model: OR = 0.868, 95% CI: 0.778 - 0.968), rs2283123 (allelic model: OR = 0.285, 95% CI: 0.095 - 0.862; dominant model: OR = 0.290, 95% CI: 0.094 -0.897) and rs2007153 (allelic model: OR = 2.196, 95% CI: 1.506 - 3.200; dominant model: OR = 2.985, 95% CI: 1.465 - 6.084; recessive model: OR = 2.729, 95% CI: 1.548 - 4.812) variants were shown to be significantly associated with the risk of AD (the former variant) and SCZ (the latter two variants).
On the one hand, most DBH polymorphisms from the currently available loci showed no linkage to AD, PD or SCZ, indicating the lower possibility of these loci serving as genetic markers of the risks of diseases with neurodegenerative characteristics. On the other hand, the DBH rs2283123 and rs2007153 polymorphisms could have opposite effects on SCZ development in Caucasians and be more specific in Croatians, while the DBH rs1611131 minor variant might have a protective effect on AD risk in Caucasians; however, these results require further study.
背景/目的：阿尔茨海默病（AD）、帕金森病（PD）和精神分裂症（SCZ）的神经病变具有不同的病理机制，但有一些共同的神经退行性特征，如神经元结构和功能的逐渐丧失。多巴胺β-羟化酶（DBH）是位于9q34染色体区域的一个基因，在多巴胺转化为去甲肾上腺素（NE）的过程中起关键作用。几项病例对照研究报道了该途径在AD、PD和SCZ发病机制中的作用。然而，结果存在争议。
我们进行了一项荟萃分析，以评估该基因多态性与AD、PD和SCZ之间的关联。检索了七个数据库（PubMed、Embase、Web of Science、中国知网（CNKI）、万方、SZ基因和AD基因）以确定符合条件的研究。计算比值比（OR）及其95%置信区间（CI），以评估DBH变异与AD、PD和SCZ易感性的关联。
我们的荟萃分析共纳入了41项研究，涉及10506例病例和15083例对照。分析结果表明，目前可用的大多数DBH多态性与神经疾病AD、PD和SCZ之间缺乏关联（P>0.05）；然而，DBH rs1611131（等位基因模型：OR = 0.889，95% CI：0.815 - 0.969；显性模型：OR = 0.868，95% CI：0.778 - 0.968）、rs2283123（等位基因模型：OR = 0.285，95% CI：0.095 - 0.862；显性模型：OR = 0.290，95% CI：0.094 - 0.897）和rs2007153（等位基因模型：OR = 2.19 6，95% CI：1.506 - 3.200；显性模型：OR = 2.985，95% CI：1.465 - 6.084；隐性模型：OR = 2.729，95% CI：1.548 - 4.812）变异显示与AD（前一个变异）和SCZ（后两个变异）的风险显著相关。
一方面，目前可用位点的大多数DBH多态性与AD、PD或SCZ无连锁关系，表明这些位点作为具有神经退行性特征疾病风险的遗传标记的可能性较低。另一方面，DBH rs2283123和rs2007153多态性可能对高加索人中SCZ的发展有相反的影响，在克罗地亚人中更具特异性，而DBH rs1611131次要变异可能对高加索人中AD风险有保护作用；然而，这些结果需要进一步研究。
