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

Matthew J. Chiocco, Xuguang Zhu, Donna Walther, Olga Pletnikova, Juan C. Troncoso, George R. Uhl, Qing Rong Liu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1809-1826
Number of pages18
JournalSubstance Use and Misuse
Volume45
Issue number11
DOIs
StatePublished - Jun 1 2010

Keywords

  • Alternative splicing
  • Gene regulation
  • Phosphatase
  • SNP association

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Health(social science)
  • Public Health, Environmental and Occupational Health
  • Psychiatry and Mental health

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