DNMT3A

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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DNMT3A

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DNMT3A
©2020 PFPC

COVID-19
"DNMT3A and TET2 mutations were by far the most common, concerning 28 (23%) and 26 patients (21%), respectively. Overall, mutations in DNMT3A and/or TET2 were present in 36% (44/122) of COVID-19 patients and were found in 80% (44/55) of those with CH. Ten patients had both DNMT3A and TET2 mutations."
(Duployez et al., 2020)

Duployez N, Demonchy J, Berthon C, Goutay J, Caplan M, Moreau AS, Bignon A, Marceau-Renaut A, Garrigue D, Raczkiewicz I, Geffroy S, Bucci M, Alidjinou K, Demaret J, Labalette M, Brousseau T, Dupont A, Rauch A, Poissy J, Susen S, Preudhomme C, Quesnel B - "Clinico-Biological Features and Clonal Hematopoiesis in Patients with Severe COVID-19" Cancers (Basel) 12(7):E1992 (2020)
https://www.mdpi.com/2072-6694/12/7/1992/htm

Fluoride

Fu M, Wu X, He J, Zhang Y, Hua S - "Natrium fluoride influences methylation modifications and induces apoptosis in mouse early embryos" Environ Sci Technol. 48(17):10398-405 (2014)
https://pubmed.ncbi.nlm.nih.gov/25102367/
(mouse embryo)

Niu Q, Liu H, Guan Z, Zeng Q, Guo S, He P, Guo L, Gao P, Xu B, Xu Z, Xia T, Wang A - "The effect of c-Fos demethylation on sodium fluoride-induced apoptosis in L-02 cells" Biol Trace Elem Res 149(1):102-9 (2012)
https://pubmed.ncbi.nlm.nih.gov/22528769/
(human embryo)

Gq/11

"At a molecular level, progression of CH to MPD is accompanied by selection for mutations activating Ras/Raf/MAPK signaling."

(Loberg et al., 2019)

Loberg MA, Bell RK, Goodwin LO, Eudy E, Miles LA, SanMiguel JM, Young K, Bergstrom DE, Levine RL, Schneider RK, Trowbridge JJ - "Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis" Leukemia 33(7):1635-1649 (2019)
https://pubmed.ncbi.nlm.nih.gov/30692594/

Thyroid
"In the mouse and other mammals, DNMT3A is a TH-induced gene, implicated not only in brain development but also in that of other tissues, including those involved in metabolic control, such as the hypothalamus and the liver."
(Demeneix, 2019)

Demeneix BA - "Evidence for Prenatal Exposure to Thyroid Disruptors and Adverse Effects on Brain Development" Eur Thyroid J 8(6):283-292 (2019)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944944/

Kvaratskhelia T, Kvaratskhelia E, Kankava K, Abzianidze E - "MTHFR GENE C677T POLYMORPHISM AND LEVELS OF DNA METHYLTRASFERASES IN SUBCLINICAL HYPOTHYROIDISM" Georgian Med News (265):19-24 (2017)
https://pubmed.ncbi.nlm.nih.gov/28574380/
"In addition, individuals with TT and CT genotypes and hypothyroidism showed elevated amount of DNMT3a in nuclear extracts of PBMC compared with controls, while no significant difference in DNMT1 levels was observed."
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