S. N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India.
Department of Genetics, University of Calcutta, Kolkata, India.
J Gene Med. 2019 Sep;21(9):e3109. doi: 10.1002/jgm.3109. Epub 2019 Jul 23.
Wilson's disease (WD) is a rare copper metabolism disorder with hepatic and neurological symptoms. Dopamine β hydroxylase (DBH) encodes a copper-dependent mono-oxygenase that converts dopamine to norepinephrine, thereby regulating the endogenous dopamine content in the neurons. Polymorphisms of DBH have been reported to be associated with several neurological diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia and attention-deficit hyperactivity disorder, which have overlapping neurological symptoms with WD. The present study aimed to assess the role of DBH polymorphisms on the clinical course of WD.
In total, 141 WD patients from India were included in the present study. Three polymorphisms of DBH (rs1611115 in the promoter, rs1108580 in exon 2 and rs129882 in 3'-UTR) were screened for their association with the clinical attributes (hepatic and neurological features) and age of onset of WD using a polymerase chain reaction-restriction fragment length polymorphsm method and sequencing approach. The distribution of genotype or allele frequencies was tested using 2 × 2 contingency chi-squared and logistic regression analysis (additive, dominant and recessive model).
The genotypic and allelic frequencies of these single nucleotide polymophisms did not vary significantly along with the clinical symptoms (hepatic and neurological) or the age of onset of WD. No significant association was observed when we analyzed our samples with respect to harboring different kinds of ATP7B mutations (nonsense/in-del and missense).
The data obtained in the present study suggest that the selected DBH variants are unlikely to have any significant contribution towards modifying the clinical symptoms of Indian WD patients.
Wilson 病(WD)是一种罕见的铜代谢紊乱疾病,具有肝和神经症状。多巴胺β羟化酶(DBH)编码一种铜依赖性单加氧酶,可将多巴胺转化为去甲肾上腺素,从而调节神经元中的内源性多巴胺含量。已报道 DBH 的多态性与几种神经疾病有关,如帕金森病、阿尔茨海默病、精神分裂症和注意缺陷多动障碍,这些疾病与 WD 具有重叠的神经症状。本研究旨在评估 DBH 多态性对 WD 临床病程的作用。
本研究共纳入 141 例来自印度的 WD 患者。使用聚合酶链反应-限制性片段长度多态性方法和测序方法筛选 DBH 的三个多态性(启动子中的 rs1611115、外显子 2 中的 rs1108580 和 3'-UTR 中的 rs129882)与 WD 的临床特征(肝和神经特征)和发病年龄的相关性。使用 2×2 列联表卡方检验和 logistic 回归分析(加性、显性和隐性模型)检验基因型或等位基因频率的分布。
这些单核苷酸多态性的基因型和等位基因频率与 WD 的临床症状(肝和神经)或发病年龄没有显著差异。当我们根据是否携带不同类型的 ATP7B 突变(无义/缺失和错义)分析我们的样本时,没有观察到显著的相关性。
本研究获得的数据表明,所选的 DBH 变体不太可能对印度 WD 患者的临床症状有任何显著影响。