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dc.contributor.authorMelo, Maria Clara C. [UNIFESP]
dc.contributor.authorde Souza, Janaina S. [UNIFESP]
dc.contributor.authorKizys, Marina M. L. [UNIFESP]
dc.contributor.authorVidi, Angela C. [UNIFESP]
dc.contributor.authorDorta, Haron S. [UNIFESP]
dc.contributor.authorKunii, Ilda S. [UNIFESP]
dc.contributor.authorGiannocco, Gisele [UNIFESP]
dc.contributor.authorCarvalheira, Gianna [UNIFESP]
dc.contributor.authorDias-da-Silva, Magnus R. [UNIFESP]
dc.date.accessioned2020-06-26T16:30:17Z
dc.date.available2020-06-26T16:30:17Z
dc.date.issued2017
dc.identifierhttp://dx.doi.org/10.1210/js.2017-00015]
dc.identifier.citationJournal Of The Endocrine Society. Washington, v. 1, n. 7, p. 809-815, 2017.
dc.identifier.issn2472-1972
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53465
dc.description.abstractThyrotoxic periodic paralysis (TPP) is a life-threatening neuromuscular complication of thyrotoxicosis characterized by muscle weakness and hypokalemia and with an unclear etiopathogenesis. However, the 17q24.3 locus had been genetically linked to TPP, in which the genetic variant rs312691 (TC genotype) in long intergenic noncoding RNA (lincRNA) CTD-2378E21.1 is located downstream of inward-rectifier potassium (Kir) channel genes [KCNJ2 and its antisense KCNJ2 (AS-KCNJ2)]. A TPP patient with a suppressed thyroid-stimulating hormone level, a high free thyroxine level of (5.8 ng/dL), and low serum potassium level of (2 mEq/L) was evaluated for Kir channel expression during and after recovery from thyrotoxicosis. We observed that circulating lincRNA and Kir expression varied in accordance with thyroid status and TC genotype. To endorse this association of a lincRNA-rs312691 variant with a genetic risk of TPP, an additional series of 37 patients with TPP and 32 patients with thyrotoxic without paralysis (TWP) were assessed. Weverified that the risk of minor allele Cwas greater in TPP than inTWP(odds ratio, 5.289en
dc.description.abstractP = 0.0062), and protective major allele T was more frequent than observed in the 1000 genome controls (odds ratio, 11.90en
dc.description.abstractP < 0.0001). AS-KCNJ2 was downregulated during thyrotoxicosis in theTWPcontrols carrying allele T and were upregulated in those with TPP with risk allele C. Moreover, KCNJ2 (Kir2.1) expression was reduced during thyrotoxicosis and restored in euthyroid status. We further excluded any other coding variant by performing targeted exome sequencing mutational screening in 17q24.3. Our data suggest that high lincRNA AS-KCNJ2 and CDT-2378E21.1 expression, possibly driven by the triiodothyronine regulatory mechanism, reduces the Kir2.1 expression observed during thyrotoxicosis. This finding could contribute to the understanding of the reduced inward-rectifying current observed during muscle weakness in genetically susceptible TPP patients. Copyright (c) 2017 Endocrine Societyen
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.description.sponsorshipSao Paulo State Research Foundation (FAPESP)
dc.format.extent809-815
dc.language.isoeng
dc.publisherEndocrine Soc
dc.relation.ispartofJournal Of The Endocrine Society
dc.rightsACESSO RESTRITO
dc.subjectthyrotoxic paralysisen
dc.subjectlincRNAen
dc.subjectKCNJ2en
dc.subjectKir channel expressionen
dc.subjectKir antisenseen
dc.titleNovel lincRNA Susceptibility Gene and Its Role in Etiopathogenesis of Thyrotoxic Periodic Paralysisen
dc.typeArtigo
dc.description.affiliationUniv Fed Sao Paulo, Lab Mol & Translat Endocrinol, Dept Med, BR-04039032 Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Biol Sci, BR-09972270 Diadema, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Mol Biol Program, BR-04044020 Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Morphol & Genet, BR-04039032 Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Lab Mol & Translat Endocrinol, Dept Med, BR-04039032 Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Biol Sci, BR-09972270 Diadema, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Mol Biol Program, BR-04044020 Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Morphol & Genet, BR-04039032 Sao Paulo, Brazil
dc.description.sponsorshipIDCAPES
dc.description.sponsorshipIDFAPESP: 2012/01628-0
dc.description.sponsorshipIDFAPESP: 2009/50575-4
dc.description.sponsorshipIDFAPESP: 2011/20747-8
dc.identifier.doi10.1210/js.2017-00015
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000425348400004
dc.coverageWashington
dc.citation.volume1]
dc.citation.issue7]


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