PEMT G523A (V175M) Is Associated with Sporadic Alzheimer's Disease in a Chinese Population

• Published in: Journal of molecular neuroscience Vol. 46; no. 3; pp. 505 - 508
• Main Authors: Bi, Xiu-Hua, Zhao, Hua-Lu, Zhang, Zhen-Xin, Zhang, Jun-Wu
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01.03.2012; Springer Nature B.V
• Subjects: Age; Aged; Alzheimer Disease - enzymology; Alzheimer Disease - ethnology; Alzheimer Disease - genetics; Alzheimer's disease; Amino Acid Substitution - genetics; Asian Continental Ancestry Group - genetics; Biomedical and Life Sciences; Biomedicine; Cell Biology; China - epidemiology; Dementia; Female; Gender; Genetic Association Studies; Homocysteine; Humans; Male; Metabolism; Middle Aged; Neurochemistry; Neurology; Neurosciences; Phosphatidylethanolamine N-Methyltransferase - genetics; Plasma; Polymorphism; Polymorphism, Single Nucleotide - genetics; Proteomics; Regression analysis; Risk Factors; Solvents; China; Beijing China; Phosphatidylethanolamine; methyltransferase; Association study; Chinese; Homocysteine; Alzheimer's disease; Polymorphism
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-011-9630-3

There is evidence that increased concentrations of circulating homocysteine are associated with Alzheimer's disease (AD). Phosphatidylethanolamine N -methyltransferase (PEMT) is an important catalyst involved in the production of homocysteine. We investigated the association of a functional single nucleotide polymorphism (rs7946) in PEMT with sporadic AD risk in a Han Chinese population that included 386 AD patients and 366 controls. PEMT G523A was genotyped by either sequencing or PCR-restriction fragment length polymorphism analysis. The plasma homocysteine concentrations of 210 subjects were determined by high-performance liquid chromatography. Significant higher frequency of the A allele was detected in AD cases than in controls (A vs. G, p  = 0.007, OR = 1.482, 95% CI 1.114–1.972). After adjusting for gender, age/age at onset, and APOE ε4 status, logistic analysis showed rs7946 was associated with AD in a dominant model (AA + GA vs. GG, p  = 0.007, OR = 1.596, 95% CI 1.138–2.240). When stratified by APOE ε4 status or gender, the significant difference was only observed in the APOE ε4 non-carriers and in the female subjects, respectively. We did not find a relationship of this polymorphism with plasma homocysteine levels. These results suggested that PEMT G523A is associated with AD and that the A allele is an APOE ε4-independent risk factor for AD among Han Chinese women.