Association between the COMTVal158Met Genotype and Alzheimer's Disease in the Han Chinese Population

Yong Ji; Zhihong Shi; Mengyuan Liu; Shuai Liu; Shuling Liu; Jinhuan Wang

doi:10.1159/000357161

Association between the COMTVal158Met Genotype and Alzheimer's Disease in the Han Chinese Population

Dement Geriatr Cogn Dis Extra. 2014 Jan 31;4(1):14-21. doi: 10.1159/000357161. eCollection 2014 Jan.

Authors

Yong Ji¹, Zhihong Shi¹, Mengyuan Liu², Shuai Liu², Shuling Liu², Jinhuan Wang¹

Affiliations

¹ Key Laboratory of Cerebral Vascular Disease and Neurodegenerative Disease, Tianjin, China ; Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China.
² Key Laboratory of Cerebral Vascular Disease and Neurodegenerative Disease, Tianjin, China.

Abstract

Background: Alzheimer's disease (AD) is the leading cause of dementia worldwide and is associated with individual, familial and social burdens. Catechol-O-methyltransferase (COMT) may have a prominent role in AD pathophysiology by affecting the metabolism of catecholamine neurotransmitters and estrogen. Although the COMT rs4680 gene polymorphism has been investigated as a susceptibility factor for AD, the results are inconsistent. The aim of this study was to examine the influence of the COMT rs4680 gene polymorphism as a risk factor for AD in the Han Chinese population and its synergistic effect with the apolipoprotein E (APOE)gene.

Methods: A total of 137 AD patients and 194 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. All subjects were analyzed for the COMTrs4680 polymorphism and APOEgenotype.

Results: No significant differences were observed between AD and control subjects regarding the COMT genotype frequencies of Val/Val, Val/Met and Met/Met, but Met alleles were higher in AD than in control subjects (35.4 and 28.1%, p = 0.045). A minor synergistic effect between the genotypes GG and APOEε4 was observed in AD patients (OR: 5.707, 95% CI: 2.505-13.002, p < 0.001). This synergistic effect was greater in women, who showed higher OR of AD (16.007, 95% CI: 4.606-56.118, p < 0.001) versus the AD group with APOE ε4 (11.972, 95% CI: 5.534-25.902, p < 0.001). Furthermore, the COMT Met allele was an independent risk factor for AD without APOE ε4 allele carriers (OR: 1.806, 95% CI: 1.160-2.810, p = 0.009), especially in men (OR: 4.904, 95% CI: 2.381-10.099, p < 0.001).

Conclusion: The COMT(Val158Met) polymorphism is not an independent risk factor for AD but shows a synergistic effect between the genotypes GG and APOEε4 that proves greater in women with AD. The COMT Met allele represents a risk factor in AD without APOE ε4 allele carriers, which is notable in men with AD.

Keywords: Alzheimer's disease; Apolipoprotein E; Catechol-O-methyltransferase; Polymorphism.