Fine Mapping of Calcineurin (<i>PPP3CA</i>) Gene Reveals Novel Alternative Splicing Patterns, Association of 5′UTR Trinucleotide Repeat With Addiction Vulnerability, and Differential Isoform Expression in Alzheimer's Disease

Chiocco, Matthew J.; Zhu, Xuguang; Walther, Donna; Pletniková, Olga; Troncoso, Juan C.; Uhl, George R.; Liu, Qingrong

doi:10.3109/10826084.2010.482449

Cited by 22 publications

(20 citation statements)

References 26 publications

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“…The Chi-square analysis used to determine p values for genotype and allele frequencies returned no statistically significant difference (p > .05) between cases and controls for rs2850328 genotype frequencies (χ 2 = 1.2, p = .5476) and allele frequencies (χ 2 = 0.68, p = .4108) which was a similar finding as Chiocco et al (2010) who also found no significance in the genotype frequencies (p = .968) or the allele frequencies (p = .962) for the same SNP in a population of addiction abusers and healthy controls.…”

Section: Twin Research and Human Genetics December 2011supporting

confidence: 66%

“…While the MARK4 rs2395 SNP to our knowledge has not been previously investigated in an association study, the PPP3CA rs2850328 SNP was previously investigated in an association study on addiction vulnerability and differential isoform expression in Alzheimer's disease (Chiocco et al, 2010). In the study, the investigators looked at several PPP3CA SNPs including rs2850328 associated with addiction for an association with Alzheimer's disease.…”

Section: Twin Research and Human Genetics December 2011mentioning

confidence: 99%

“…The primers used for the PPP3CA SNP (rs2850328) were taken from the Chiocco et al (2010) study with the following sequences: forward-CTCGCGTTCATTGGCTA-GAG and reverse-GCAAAAGTGACACCTGAGCA. The primers used for the MARK4 SNP (rs2395) were designed using Primer Express 3.0 (Applied Biosystems) and had the following sequences: forward-GCAGCCTGTTGCC-CAATAA and reverse-TGGATTCCCACGCCTCTTC.…”

Section: Genotypingmentioning

confidence: 99%

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Investigation of Two Wnt Signalling Pathway Single Nucleotide Polymorphisms in a Breast Cancer-Affected Australian Population

et al. 2011

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In the mammary gland, Wnt signals are strongly implicated in initial development of the mammary rudiments and in the ductal branching and alveolar morphogenesis that occurs during pregnancy. Previously, we identified two Wnt signaling pathway-implicated genes, PPP3CA and MARK4, as having a role in more aggressive and potentially metastatic breast tumors. In this study, we examined two SNPs within PPP3CA and MARK4 in an Australian case-control study population for a potential role in human breast cancers. 182 cases and 180 controls were successfully genotyped for the PPP3CA SNP (rs2850328) and 182 cases and 177 controls were successfully genotyped for the MARK4 SNP (rs2395) using High Resolution Melt (HRM) analysis. Genotypes of randomly selected samples for both SNPs were validated by dye terminator sequencing. Chi-square tests were performed to determine any significant differences in the genotype and allele frequencies between the cases and controls. Chi-square analysis showed no statistically significant difference (ρ > .05) for genotype frequencies between cases and controls for rs2850328 (χ2 = 1.2, p = .5476) or rs2395 (χ2 = .3, p = .8608). Similarly, no statistical difference was observed for allele frequencies for rs2850328 (χ2 = .68, p = .4108) or rs2395 (χ2 = .02, p = .893). Even though an association of the polymorphisms rs2850328 and rs2395 and breast cancer was not detected in our case-control study population, other variants within the PPP3CA and MARK4 genes may still be associated with breast cancer, as both genes are implicated with processes involved in the disease as well as their mutual partaking in the Wnt signaling pathway.

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Section: Twin Research and Human Genetics December 2011supporting

confidence: 66%

Section: Twin Research and Human Genetics December 2011mentioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

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Investigation of Two Wnt Signalling Pathway Single Nucleotide Polymorphisms in a Breast Cancer-Affected Australian Population

et al. 2011

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“…A detailed analysis has identified a variety of novel PPP3CA variants that can generate a number of splicing isoforms of PP2B that exhibit differential expression in brain and nonbrain tissues. 118 The expression of several of these PPP3CA isoforms, but not all, that encode functional phosphatase domains was found to be decreased in the medial temporal gyrus from AD patient brains.…”

Section: Protein Phosphatase 2b (Calcineurin)mentioning

confidence: 91%

Protein Phosphatases and Alzheimer's Disease

Braithwaite

Stock

Lombroso

et al. 2012

Progress in Molecular Biology and Translational Science

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Alzheimer’s Disease (AD) is characterized by progressive loss of cognitive function, linked to marked neuronal loss. Pathological hallmarks of the disease are the accumulation of the amyloid-β (Aβ) peptide in the form of amyloid plaques and the intracellular formation of neurofibrillary tangles (NFTs). Accumulating evidence supports a key role for protein phosphorylation in both the normal and pathological actions of Aβ as well as the formation of NFTs. NFTs contain hyperphosphorylated forms of the microtubule-binding protein tau, and phosphorylation of tau by several different kinases leads to its aggregation. The protein kinases involved in the generation and/or actions of tau or Aβ are viable drug targets to prevent or alleviate AD pathology. However, it has also been recognized that the protein phosphatases that reverse the actions of these protein kinases are equally important. Here, we review recent advances in our understanding of serine/threonine and tyrosine protein phosphatases in the pathology of AD.

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“…PPP3CA encodes the alpha catalytic subunit of a Ca2+/calmodulin-dependent serine/threonine phosphatase, which is also called calcineurin. Genetic alterations in PPP3CA have been previously linked with vulnerability to misuse of multiple substances (Chiocco et al, 2010). It was reported that calcineurin may influence reward-and memory-related phenotypes in addiction thought to link dopaminergic and glutamatergic signals (Chiocco et al, 2010;Gerdjikov & Beninger, 2005).…”

mentioning

confidence: 99%

DISC1 as a Possible Genetic Contribution to Opioid Dependence in a Polish Sample

Fudalej

Jakubczyk

Piwoński

et al. 2016

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Disrupted-in-schizophrenia 1 (DISC1) has been linked to vulnerability to a variety of psychiatric disorders and neuropsychiatric phenotypes. However, DISC1 has not been frequently examined as a potential risk factor for substance dependence. An association between opioid dependence and DISC1 rs2738888 polymorphism has been recently reported. In addition, opioid dependence was associated with rs6419156 located close to the protein phosphatase 3 catalytic subunit alpha isoform (PPP3CA) gene. The aim of the present study was to examine the associations between opioid dependence with rs2738888 and rs6419156 in an independent sample. Method: The selected polymorphisms were genotyped in a sample of 392 individuals (69.9% male) diagnosed as alcohol-and/or opioid-dependent. A control group (n = 257; 67.7% male) was derived from the Polish National Health Survey (N = 14,350). Results: The frequency of rs2738888 C allele was higher in controls than in opioid-dependent cases (OR = 0.65, p = .045). Phenotypic-oriented analyses performed within opioiddependent individuals revealed the association between lifetime suicide attempt and rs2738888. The C allele of rs2738888 had a protective effect on lifetime suicide attempt in opioid-dependent patients (OR = 0.25, p = .003). Rs6419156 was not associated with substance dependence in the examined sample. Conclusions: The DISC1 may play an important role in vulnerability to opioid dependence. In addition, DISC1 may also be a genetic risk factor for suicide attempt in opioid-dependent individuals.

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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

Cited by 22 publications

References 26 publications

Investigation of Two Wnt Signalling Pathway Single Nucleotide Polymorphisms in a Breast Cancer-Affected Australian Population

Investigation of Two Wnt Signalling Pathway Single Nucleotide Polymorphisms in a Breast Cancer-Affected Australian Population

Protein Phosphatases and Alzheimer's Disease

DISC1 as a Possible Genetic Contribution to Opioid Dependence in a Polish Sample

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