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.
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.
Chiocco
Matthew J
MJ
Molecular Neurobiology Branch, NIH-IRP, NIDA, DHHS, Baltimore, MD 21224, USA.
Zhu
Xuguang
X
Walther
Donna
D
Pletnikova
Olga
O
Troncoso
Juan C
JC
Uhl
George R
GR
Liu
Qing-Rong
QR
D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016739:Behavior, Addictive / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D019703:Calcineurin / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D012313:RNA; D018911:Trinucleotide Repeats
D020121:5' Untranslated Regions; D020033:Protein Isoforms; D012313:RNA; D019703:Calcineurin; C525673:PPP3CA protein, human