Title:Association of the MAOB rs1799836 Single Nucleotide Polymorphism and APOE ε4 Allele in Alzheimer’s Disease
Volume: 18
Issue: 7
关键词:
阿尔茨海默病、MAOB、APOE、多态性、遗传生物标志物、轻度认知障碍。
摘要:
Background: The dopaminergic system is functionally compromised in Alzheimer’s
Disease (AD). The activity of Monoamine Oxidase B (MAOB), the enzyme involved in the degradation
of dopamine, is increased during AD. Also, increased expression of MAOB occurs in the
postmortem hippocampus and neocortex of patients with AD. The MAOB rs1799836 polymorphism
modulates MAOB transcription, consequently influencing protein translation and MAOB activity.
We recently showed that cerebrospinal fluid levels of amyloid β1-42 are decreased in patients
carrying the A allele in MAOB rs1799836 polymorphism.
Objective: The present study compares MAOB rs1799836 polymorphism and APOE, the only confirmed
genetic risk factor for sporadic AD.
Methods: We included 253 participants, 127 of whom had AD, 57 had mild cognitive impairment,
11 were healthy controls, and 58 suffered from other primary causes of dementia. MAOB and
APOE polymorphisms were determined using TaqMan SNP Genotyping Assays.
Results: We observed that the frequency of APOE ε4/ε4 homozygotes and APOE ε4 carriers is significantly
increased among patients carrying the AA MAOB rs1799836 genotype.
Conclusion: These results indicate that the MAOB rs1799836 polymorphism is a potential genetic
biomarker of AD and a potential target for the treatment of decreased dopaminergic transmission
and cognitive deterioration in AD.