Gołab-Janowska Monika, Honczarenko Krystyna, Gawrońska-Szklarz Barbara, Potemkowski Andrzej
Katedra i Klinika Neurologii, Pomorskiej Akademia Medyczna, Szczecin.
Neurol Neurochir Pol. 2007 Mar-Apr;41(2):113-21.
The theory of multifactorial inheritance is considered in the pathogenesis of sporadic Alzheimer's disease (AD) and Parkinson's disease (PD); therefore, it makes the genes regulating bioactivation or detoxification of exogenous substances candidates of sensitivity to Alzheimer's and Parkinson's diseases. The aims of the study were: 1) to determine the genotypes of CYP2D6 cytochrome (CYP2D6) in patients with AD and sporadic PD with dementia; 2) to evaluate the relationship between the CYP2D6 genotype and the age of onset of the disease, the extent of dementia in AD and PD, the dose and side effects of L-dopa in PD; 3) to evaluate the usefulness of CYP2D6 genotyping in predicting predispositions to PD and AD.
53 patients with AD aged 58-84 (mean age 72.6) and 52 patients with PD with dementia aged 51-82 (mean age 70.4) were recruited. Each AD patient satisfied criteria for probable AD. Diagnostic and Statistical Manual of Mental Disorders 4th edition, Mini-Mental State Examination, Clinical Dementia Rating Scale and Global Deterioration Scale were used for dementia evaluation in PD patients. Clinical scales for PD evaluation were used. Methods of molecular biology were used for genetic studies.
There were no differences in CYP2D6 genotype and allele distribution in AD and PD patients. There was no relationship between CYP2D6 alleles and the age of onset and advancement of dementia in AD and PD. No relationship between CYP2D6 alleles and the dose and side effects of L-dopa in patients with sporadic PD with dementia was observed.
As there were no differences in CYP2D6 polymorphism in AD and PD, CYP2D6 does not seem to be a factor predisposing to these diseases.
散发性阿尔茨海默病(AD)和帕金森病(PD)的发病机制考虑多因素遗传理论;因此,调节外源性物质生物活化或解毒的基因成为对阿尔茨海默病和帕金森病敏感的候选基因。本研究的目的是:1)确定AD患者和伴有痴呆的散发性PD患者中细胞色素CYP2D6(CYP2D6)的基因型;2)评估CYP2D6基因型与疾病发病年龄、AD和PD中痴呆程度、PD中左旋多巴剂量及副作用之间的关系;3)评估CYP2D6基因分型在预测PD和AD易感性方面的实用性。
招募了53例年龄在58 - 8岁(平均年龄72.6岁)的AD患者和52例年龄在51 - 82岁(平均年龄)的伴有痴呆的PD患者。每位AD患者均符合可能AD的标准。使用《精神障碍诊断与统计手册》第4版、简易精神状态检查表、临床痴呆评定量表和总体衰退量表对PD患者进行痴呆评估。使用PD评估的临床量表。采用分子生物学方法进行基因研究。
AD和PD患者中CYP2D6基因型和等位基因分布无差异。CYP2D6等位基因与AD和PD中痴呆的发病年龄及进展无关。未观察到CYP2D6等位基因与伴有痴呆的散发性PD患者中左旋多巴剂量及副作用之间的关系。
由于AD和PD中CYP2D6多态性无差异,CYP2D6似乎不是这些疾病的易感因素。