Synonymous mutation rs1129293 is associated with PIK3CG expression and PI3K gamma activation in patients with chronic Chagas cardiomyopathy

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorSILVA, Maria Claudia
dc.contributor.authorFUZO, Carlos Alessandro
dc.contributor.authorPAIVA, Isadora Marques
dc.contributor.authorBIBO, Naira Lopes
dc.contributor.authorOLIVEIRA, Maykon Tavares de
dc.contributor.authorSOARES, Hellen Anastacia da Silva
dc.contributor.authorCHEVILLARD, Christophe
dc.contributor.authorKALIL, Jorge
dc.contributor.authorCUNHA-NETO, Edecio
dc.contributor.authorCUNHA, Thiago Mattar
dc.contributor.authorSILVA, Joao Santana
dc.date.accessioned2022-12-21T13:17:53Z
dc.date.available2022-12-21T13:17:53Z
dc.date.issued2022
dc.description.abstractSingle nucleotide polymorphisms (SNPs) that do not change the composition of amino acids and cause synonymous mutations (sSNPs) were previously considered to lack any functional roles. However, sSNPs have recently been shown to interfere with protein expression owing to a myriad of factors related to the regulation of transcription, mRNA stability, and protein translation processes. In patients with Chagas disease, the presence of the synonymous mutation rs1129293 in phosphatidylinositol-4,5-bisphosphate 3-kinase gamma (PIK3CG) gene contributes to the development of the chronic Chagas cardiomyopathy (CCC), instead of the digestive or asymptomatic forms. In this study, we aimed to investigate whether rs1129293 is associated with the transcription of PIK3CG mRNA and its activity by quantifying AKT phosphorylation in the heart samples of 26 chagasic patients with CCC. Our results showed an association between rs1129293 and decreased PIK3CG mRNA expression levels in the cardiac tissues of patients with CCC. The phosphorylation levels of AKT, the protein target of PI3K, were also reduced in patients with this mutation, but were not correlated with PI3KCG mRNA expression levels. Moreover, bioinformatics analysis showed that rs1129293 and other SNPs in linkage disequilibrium (LD) were associated with the transcriptional regulatory elements, post-transcriptional modifications, and cell-specific splicing expression of PIK3CG mRNA. Therefore, our data demonstrates that the synonymous SNP rs1129293 is capable of affecting the PIK3CG mRNA expression and PI3K gamma activation.eng
dc.description.indexMEDLINEeng
dc.identifier.citationIMMUNOBIOLOGY, v.227, n.5, article ID 152242, 7p, 2022
dc.identifier.doi10.1016/j.imbio.2022.152242
dc.identifier.eissn1878-3279
dc.identifier.issn0171-2985
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/50408
dc.language.isoeng
dc.publisherELSEVIER GMBHeng
dc.relation.ispartofImmunobiology
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright ELSEVIER GMBHeng
dc.subjectSynonymous mutationeng
dc.subjectChagas diseaseeng
dc.subjectPI3K?eng
dc.subjectSingle nucleotide polymorphismeng
dc.subjectrs1129293eng
dc.subject.othervirus infectioneng
dc.subject.otheralterseng
dc.subject.otherakteng
dc.subject.wosImmunologyeng
dc.titleSynonymous mutation rs1129293 is associated with PIK3CG expression and PI3K gamma activation in patients with chronic Chagas cardiomyopathyeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryFrança
hcfmusp.affiliation.countryisofr
hcfmusp.author.externalSILVA, Maria Claudia:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalFUZO, Carlos Alessandro:Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalPAIVA, Isadora Marques:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalBIBO, Naira Lopes:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalOLIVEIRA, Maykon Tavares de:Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Internal Med, Cardiol Div, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalSOARES, Hellen Anastacia da Silva:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalCHEVILLARD, Christophe:Aix Marseille Univ, Inst MarMaRa, INSERM, TAGC Theories & Approaches Genom Complex,UMR 1090, Marseille, France
hcfmusp.author.externalCUNHA, Thiago Mattar:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP, Brazil
hcfmusp.author.externalSILVA, Joao Santana:Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP, Brazil; Fiocruz Biinst Translat Med Platform, Bandeirantes Ave 3900, BR-14049900 Ribeirao Preto, SP, Brazil
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcJORGE ELIAS KALIL FILHO
hcfmusp.contributor.author-fmusphcEDECIO CUNHA NETO
hcfmusp.description.articlenumber152242
hcfmusp.description.issue5
hcfmusp.description.volume227
hcfmusp.origemWOS
hcfmusp.origem.pubmed35870262
hcfmusp.origem.scopus2-s2.0-85134651803
hcfmusp.origem.wosWOS:000862545600002
hcfmusp.publisher.cityMUNICHeng
hcfmusp.publisher.countryGERMANYeng
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