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    Subst Use Misuse. 2010 Sep;45(11):1809-26. doi: 10.3109/10826084.2010.482449.

    Fine mapping of calcineurin (PPP3CA) gene reveals novel alternative splicing patterns, association of 5'UTR trinucleotide repeat with addiction vulnerability, and differential isoform expression in Alzheimer's disease.

    Chiocco MJ, Zhu X, Walther D, Pletnikova O, Troncoso JC, Uhl GR, Liu QR.

    Source

    Molecular Neurobiology Branch, NIH-IRP, NIDA, DHHS, Baltimore, MD 21224, USA.

    Abstract

    Fine mapping of calcineurin (PPP3CA) gene identified single nucleotide polymorphisms (SNPs) and simple sequence repeat polymorphisms that are associated with addiction vulnerability. A trinucleotide repeat marker, located in the 5'untranslated region (5'UTR) of the PPP3CA mRNA, exhibited significantly different genotype and allele frequencies between abusers and controls in the NIDA African-American sample. The polymorphism showed allelic-specific expression in mRNA extracted from postmortem brain specimens. Novel alternatively spliced isoforms of PPP3CA were identified and their expressions were found altered in brain regions of postmortem Alzheimer's disease patients. These data underscore the importance of calcineurin gene in the molecular mechanism of addiction and Alzheimer's diseases.

    PMID:
    20590401
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC3031160
    Free PMC Article

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