Linkage disequilibrium and haplotype analysis of the ATP7B gene in alzheimer's disease

Rosanna Squitti, Renato Polimanti, Serena Bucossi, Mariacarla Ventriglia, Stefania Mariani, Dario Manfellotto, Fabrizio Vernieri, Emanuele Cassetta, Francesca Ursini, Paolo Maria Rossini

Research output: Contribution to journalArticle

Abstract

Copper dyshomeostasis leading to a labile Cu2+ not bound to ceruloplasmin ("free" copper) may influence Alzheimer's disease (AD) onset or progression. To investigate this hypothesis, we investigated ATP7B, the gene that controls copper excretion through the bile and concentrations of free copper in systemic circulation. Our study analyzed informative ATP7B single-nucleotide polymorphisms (SNPs) in a case-control population (n=515). In particular, we evaluated the genetic structure of the ATP7B gene using the HapMap database and carried out a genetic association investigation. Linkage disequilibrium (LD) analysis highlighted that our informative SNPs and their LD SNPs covered 96% of the ATP7B gene sequence, distinguishing two "strong LD" blocks. The first LD block contains the gene region encoding for transmembrane and copper-binding, whereas the second LD block encodes for copper-binding domains. The genetic association analysis showed significant results after multiple testing correction for all investigated variants (rs1801243, odds ratio [OR]=1.52, 95% confidence interval [CI]=1.10-2.09, p=0.010; rs2147363, OR=1.58, 95% CI=1.11-2.25, p=0.010; rs1061472, OR=1.73, 95% CI=1.23-2.43, p=0.002; rs732774, OR=2.31, 95% CI=1.41-3.77, p

Original languageEnglish
Pages (from-to)3-10
Number of pages8
JournalRejuvenation Research
Volume16
Issue number1
DOIs
Publication statusPublished - Feb 1 2013

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

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    Squitti, R., Polimanti, R., Bucossi, S., Ventriglia, M., Mariani, S., Manfellotto, D., Vernieri, F., Cassetta, E., Ursini, F., & Rossini, P. M. (2013). Linkage disequilibrium and haplotype analysis of the ATP7B gene in alzheimer's disease. Rejuvenation Research, 16(1), 3-10. https://doi.org/10.1089/rej.2012.1357