Association between the catechol-O-methyltransferase polymorphism Val158Met and Alzheimer's disease in a Japanese population

作者：Shibata Nobuto^*; Nagata Tomoyuki; Tagai Kenji; Shinagawa Shunichiro; Ohnuma Tohru; Kawai Eri; Kasanuki Koji; Shimazaki Hiromi; Toda Aiko; Tagata Yuko; Nakada Tomoko; Nakayama Kazuhiko; Yamada Hisashi; Arai Heii

来源：International Journal of Geriatric Psychiatry, 2015, 30(9): 927-933.

DOI：10.1002/gps.4237

• catechol-O-methyltransferase
• apolipoprotein E
• polymorphism
• alcohol
• Alzheimer's disease
• single photon-emission computed tomography

Objective: Catechol-O-methyltransferase (COMT) plays an important role in dopamine degradation, which is associated with the pathophysiology of Alzheimer's disease (AD) and alcoholism. A functional COMT polymorphism, Val158Met (rs4680 G>A), affects the onset of AD and is associated with alcohol dependence through dopamine receptor sensitivity in the prefrontal cortex.
Methods: The aim of this case-control study (398 cases and 149 controls) was to investigate whether Val158Met polymorphism influences the onset of AD stratified according to alcohol consumption and apolipoprotein E (APOE) status. We also used single photon-emission computed tomography (SPECT) to analyse 26 patients with AD with the polymorphism.
Results: As a function of APOE status, the genotypic frequencies of rs4680 in patients with AD did not differ from those in controls. We detected a significant association between high alcohol consumption in patients with AD (HAC-AD group) and the polymorphism in genotypic and allelic frequencies. Logistic regression analyses demonstrated that the presence of the APOE genotype with rs4680 increased the risk for HAC-AD synergistically. Hyperperfusion in the right sub-lobar insula of patients with the G/G genotype was found compared with that of patients with the G/A genotype. SPECT studies showed a relationship between the polymorphism and compensatory reactions for dysfunctions of dopaminergic neurotransmission in AD pathophysiology.
Conclusion: Although genetic association between the polymorphism and the onset of AD in a Japanese population were not observed, the polymorphism affected the risk for HAC-AD.

• 出版日期2015-9