title: Genetic variability in copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with Alzheimer's disease in a Chinese population.
abstract: Previous experiments demonstrated that transgenic mice carrying both amyloid precursor protein and mutant ATP7B transgenes reduce amyloid plaques and diminish plasma Abeta levels. These experiments showed that a structural change of ATP7B may affect Alzheimers disease (AD) susceptibility. In this study three missense SNPs in ATP7B gene (rs1801243, rs1801244, and rs1801249) were chosen to test whether they were associated with AD. We tested this hypothesis using a case control design. The experimental data showed that there was a significant deviation from Hardy-Weinberg equilibrium (HWE) for SNP rs1801249 (c.3419 T greater than C, Val1140Ala) in the case group (p = 0.014) but not in the control group and that there was an association between SNP rs1801249 and AD under a recessive model (p = 0.003). The data also showed that the genotype frequency distribution of the ATP7B c.1366 G greater than C polymorphism (rs1801244, Val456Leu) differed significantly between the AD patients and the normal subjects (p = 0.012). In addition, the frequency of the TGC haplotype of SNPs rs1801243, rs1801244, and rs1801249 was significantly higher in the AD patients compared with the normal subjects (p = 8.49×10-7). These observations suggested that genetic variations in the copper transporter gene ATP7B might contribute to AD pathogenesis in the Taiwanese population.
authors.affiliation: Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.
authors.forename: H P
authors.initials: HP
authors.lastname: Liu
authors.forename: W Y
authors.initials: WY
authors.lastname: Lin
authors.forename: W F
authors.initials: WF
authors.lastname: Wang
authors.forename: C H
authors.initials: CH
authors.lastname: Tsai
authors.forename: W C
authors.initials: WC
authors.lastname: Wu
authors.forename: M T
authors.initials: MT
authors.lastname: Chiou
authors.forename: C P
authors.initials: CP
authors.lastname: Shen
authors.forename: B T
authors.initials: BT
authors.lastname: Wu
authors.forename: F J
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide
chemical_list: D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases