دورية أكاديمية
Novel lincRNA Susceptibility Gene and Its Role in Etiopathogenesis of Thyrotoxic Periodic Paralysis.
| العنوان: | Novel lincRNA Susceptibility Gene and Its Role in Etiopathogenesis of Thyrotoxic Periodic Paralysis. |
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| المؤلفون: | Melo MCC; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo, 04039-032, Brazil., de Souza JS; Biological Sciences, Universidade Federal de São Paulo, Diadema, 09972-270, Brazil., Kizys MML; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo, 04039-032, Brazil., Vidi AC; Molecular Biology Program, Universidade Federal de São Paulo, São Paulo, 04044-020, Brazil., Dorta HS; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo, 04039-032, Brazil., Kunii IS; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo, 04039-032, Brazil., Giannocco G; Molecular Biology Program, Universidade Federal de São Paulo, São Paulo, 04044-020, Brazil., Carvalheira G; Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, 04039-032, Brazil., Dias-da-Silva MR; Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo, 04039-032, Brazil.; Biological Sciences, Universidade Federal de São Paulo, Diadema, 09972-270, Brazil. |
| المصدر: | Journal of the Endocrine Society [J Endocr Soc] 2017 Feb 28; Vol. 1 (7), pp. 809-815. Date of Electronic Publication: 2017 Feb 28 (Print Publication: 2017). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Endocrine Society Country of Publication: United States NLM ID: 101697997 Publication Model: eCollection Cited Medium: Print ISSN: 2472-1972 (Print) Linking ISSN: 24721972 NLM ISO Abbreviation: J Endocr Soc Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : Endocrine Society, [2017]- |
| مستخلص: | Thyrotoxic 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. We verified that the risk of minor allele C was greater in TPP than in TWP (odds ratio, 5.289; P = 0.0062), and protective major allele T was more frequent than observed in the 1000 genome controls (odds ratio, 11.90; P < 0.0001). AS-KCNJ2 was downregulated during thyrotoxicosis in the TWP controls 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. |
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| فهرسة مساهمة: | Keywords: KCNJ2; Kir antisense; Kir channel expression; lincRNA; thyrotoxic paralysis |
| تواريخ الأحداث: | Date Created: 20171222 Latest Revision: 20201001 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5686567 |
| DOI: | 10.1210/js.2017-00015 |
| PMID: | 29264532 |
| قاعدة البيانات: | MEDLINE |
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