The role of the AKT1 gene in the Pathogenesis of type 2 diabetes mellitus and its complications
- Authors: Kochetova O.V.1,2, Shangareeva Z.A.2, Avsaleydiniva D.S.2, Viktorova T.V.2, Korytina G.F.1,2
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Affiliations:
- Institute of Biochemistry and Genetics – a structural subdivision of the Federal State Budgetary Scientific Institution of the Ufa Federal Research Center of the Russian Academy of Sciences
- Bashkir State Medical University
- Issue: Vol 22, No 3 (2024)
- Pages: 57-64
- Section: Reviews
- URL: https://journals.eco-vector.com/1728-2918/article/view/633671
- DOI: https://doi.org/10.29296/24999490-2024-03-09
- ID: 633671
Cite item
Abstract
Introduction. Type 2 diabetes (T2D) is a chronic metabolic disorder. The number of diabetic people is increasing. AKT1 is a protein kinase and a participant in the PI3K/AKT/mTOR signaling pathway. The aim of the study was to analyze the association of polymorphic variants rs3803300 and rs2494732 of the AKT1 gene with the risk of developing type 2 diabetes and its complications.
Methods. PCR-RFLP analysis was used to study polymorphic variants of two polymorphic loci of the AKT1 gene. DNA samples of 533 patients with T2D and 397 individuals of the control group were used in the work.
Results. The association of the rs3803300 locus of the AKT1 gene with the risk of developing T2D, the effect allele T (р=0.02), and the risk genotypes of CT-CC of the rs2494732 locus of the AKT1 gene (р=0.042) were revealed. It was shown that carriers of the CT-CC genotypes of the rs2494732 locus of the AKT1 gene had an increased weight (р=0.026). An association of the rs3803300 locus of the AKT1 gene with the risk of developing diabetic retinopathy (р=0.021), polyneuropathy (р=0.0084), coronary heart disease (р=0.032) and diabetic encephalopathy (р=0.0064) was found. The rs2494732 locus of the AKT1 gene is associated with the development of diabetic nephropathy (р=0.024).
Conclusion. The data obtained indicate the prospects of analyzing the PI3K/AKT/mTOR signaling pathway genes for the search for personalized predictors of T2D and its complications.
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About the authors
Olga V. Kochetova
Institute of Biochemistry and Genetics – a structural subdivision of the Federal State Budgetary Scientific Institution of the Ufa Federal Research Center of the Russian Academy of Sciences; Bashkir State Medical University
Email: Olga_mk78@mail.ru
ORCID iD: 0000-0003-2071-0969
Senior Researcher of Institute of Biochemistry and Genetics, PhD
Russian Federation, Prospekt Oktyabrya, 71, Ufa, 450054; Lenina, 3, Ufa, 450008
Ziliya A. Shangareeva
Bashkir State Medical University
Email: shangareeva2001@mail.ru
ORCID iD: 0000-0001-8745-9989
Associate Professor at the Faculty of pediatrics with courses in pediatrics, neonatology and a simulation center, PhD
Russian Federation, Lenina, 3, Ufa, 450008Diana S. Avsaleydiniva
Bashkir State Medical University
Email: ecolab_203@mail.ru
ORCID iD: 0000-0002-1590-6433
Associate Professor at the Department of Endocrinology, PhD
Russian Federation, Lenina, 3, Ufa, 450008Tatiana V. Viktorova
Bashkir State Medical University
Email: t_vict@mail.ru
ORCID iD: 0000-0001-8900-2480
Head of the Department of Biology, PhD
Russian Federation, Lenina, 3, Ufa, 450008Gulnas F. Korytina
Institute of Biochemistry and Genetics – a structural subdivision of the Federal State Budgetary Scientific Institution of the Ufa Federal Research Center of the Russian Academy of Sciences; Bashkir State Medical University
Author for correspondence.
Email: guly_kory@mail.ru
ORCID iD: 0000-0002-1695-5173
SPIN-code: 1200-2906
Expert scientific worker of Institute of Biochemistry and Genetics, Doctor of biological sciences
Russian Federation, Prospekt Oktyabrya, 71, Ufa, 450054; Lenina, 3, Ufa, 450008References
- King D., Yeomanson D., Bryant H.E. PI3King the lock: targeting the PI3K/Akt/mTOR pathway as a novel therapeutic strategy in neuroblastoma. J. Pediatr Hematol Oncol. 2015; 37 (4): 245–51. doi: 10.1097/MPH.0000000000000329
- Eshaghi F.S., Ghazizadeh H., Kazami-Nooreini S., Timar A., Esmaeily H., Mehramiz M., Avan A., Ghayour-Mobarhan M. Association of a genetic variant in AKT1 gene with features of the metabolic syndrome. Genes Dis. 2019; 6 (3): 290–5. doi: 10.1016/j.gendis.2019.03.002
- Zhang M., Yang J., Zhao X., Zhao Y., Zhu S. Network pharmacology and molecular docking study on the active ingredients of qidengmingmu capsule for the treatment of diabetic retinopathy. Sci Rep. 2021; 11 (1): 7382. doi: 10.1038/s41598-021-86914-8
- Busaidy N.L., Farooki A., Dowlati A., Perentesis J.P., Dancey J.E., Doyle L.A., Brell J.M., Siu L.L. Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J. Clin. Oncol. 2012; 30 (23): 2919–28. doi: 10.1200/JCO.2011.39.7356
- Piao Y., Li Y., Xu Q., Liu J.W., Xing C.Z., Xie X.D., Yuan Y. Association of MTOR and AKT Gene Polymorphisms with Susceptibility and Survival of Gastric Cancer. PLoS One. 2015; 10 (8): e0136447. doi: 10.1371/journal.pone.0136447
- Zhang X., Chen X., Zhai Y., Cui Y., Cao P., Zhang H., Wu Z., Li P., Yu L., Xia X., He F., Zhou G. Combined effects of genetic variants of the PTEN, AKT1, MDM2 and p53 genes on the risk of nasopharyngeal carcinoma. PLoS One. 2014; 14; 9 (3): e92135. doi: 10.1371/journal.pone.0092135
- Saravani M., Shahraki-Ghadimi H., Maruei-Milan R., Mehrabani M., Mirzamohammadi S., Nematollahi M.H. Effects of the mTOR and AKT genes polymorphisms on systemic lupus erythematosus risk. Mol Biol Rep. 2020; 47 (5): 3551–6. doi: 10.1007/s11033-020-05446-y
- Kochetova O.V., Avzaletdinova D.S., Korytina G.F., Morugova T.V., Mustafina O.E. The association between eating behavior and polymorphisms in GRIN2B, GRIK3, GRIA1 and GRIN1 genes in people with type 2 diabetes mellitus. Mol Biol Rep. 2020; 47 (3): 2035–46. doi: 10.1007/s11033-020-05304-x
- Boyle A.P., Hong E.L., Hariharan M, Cheng Y, Schaub MA, Kasowski M, Karczewski KJ, Park J, Hitz BC, Weng S, Cherry JM, Snyder M. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 2012; 22 (9): 1790–7. doi: 10.1101/gr.137323.112
- Carithers L.J., Ardlie K., Barcus M., Branton P.A., Britton A., Buia S.A., Compton C.C., DeLuca D.S., Peter-Demchok J., Gelfand E.T., Guan P., Korzeniewski G.E., Lockhart N.C., Rabiner C.A., Rao A.K., Robinson K.L., Roche N.V., Sawyer S.J., Segrè A.V., Shive C.E., Smith A.M., Sobin L.H., Undale A.H., Valentino K.M., Vaught J., Young T.R., Moore H.M. GTEx Consortium. A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project. Biopreserv Biobank. 2015; 13 (5): 311–9. doi: 10.1089/bio.2015.0032
- Gene Ontology Consortium; Aleksander S.A., Balhoff J., Carbon S., Cherry J.M., Drabkin H.J., Ebert D., Feuermann M., Gaudet P., Harris N.L., Hill D.P., Lee R., Mi H., Moxon S., Mungall C.J., Muruganugan A., Mushayahama T., Sternberg P.W., Thomas P.D., Van Auken K., Ramsey J., Siegele D.A., Chisholm R.L., Fey P., Aspromonte M.C., Nugnes M.V., Quaglia F., Tosatto S., Giglio M., Nadendla S., Antonazzo G., Attrill H., Dos Santos G., Marygold S., Strelets V., Tabone C.J., Thurmond J., Zhou P., Ahmed S.H., Asanitthong P., Luna Buitrago D., Erdol M.N., Gage M.C., Ali Kadhum M., Li K.Y.C., Long M., Michalak A., Pesala A., Pritazahra A., Saverimuttu S.C.C., Su R., Thurlow K.E., Lovering R.C., Logie C., Oliferenko S., Blake J., Christie K., Corbani L., Dolan M.E., Drabkin H.J., Hill D.P., Ni L., Sitnikov D., Smith C., Cuzick A., Seager J., Cooper L., Elser J., Jaiswal P., Gupta P., Jaiswal P., Naithani S., Lera-Ramirez M., Rutherford K., Wood V., De Pons J.L., Dwinell M.R., Hayman G.T., Kaldunski M.L., Kwitek A.E., Laulederkind S.J.F., Tutaj M.A., Vedi M., Wang S.J., D’Eustachio P., Aimo L., Axelsen K., Bridge A., Hyka-Nouspikel N., Morgat A., Aleksander S.A., Cherry J.M., Engel S.R., Karra K., Miyasato S.R., Nash R.S., Skrzypek M.S., Weng S., Wong E.D., Bakker E., Berardini T.Z., Reiser L., Auchincloss A., Axelsen K., Argoud-Puy G., Blatter M.C., Boutet E., Breuza L., Bridge A., Casals-Casas C., Coudert E., Estreicher A., Livia Famiglietti M., Feuermann M., Gos A., Gruaz-Gumowski N., Hulo C., Hyka-Nouspikel N., Jungo F., Le Mercier P., Lieberherr D., Masson P., Morgat A., Pedruzzi I., Pourcel L., Poux S., Rivoire C., Sundaram S., Bateman A., Bowler-Barnett E., Bye-A-Jee H., Denny P., Ignatchenko A., Ishtiaq R., Lock A., Lussi Y., Magrane M., Martin M.J., Orchard S., Raposo P., Speretta E., Tyagi N., Warner K., Zaru R., Diehl A.D., Lee R., Chan J., Diamantakis S., Raciti D., Zarowiecki M., Fisher M., James-Zorn C., Ponferrada V., Zorn A., Ramachandran S., Ruzicka L., Westerfield M. The Gene Ontology knowledgebase in 2023. Genetics. 2023; 224 (1): iyad031. doi: 10.1093/genetics/iyad031
- Циркин В.И., Коротаева Ю.В. Участие протеинкиназ а, в, с и d в регуляции сократимости кардиомиоцитов (обзор. Сообщение II). Журнал медико-биологических исследований. 2015; 3: 55–65. [Cirkin V.I., Korotaeva J.V. Uchastie proteinkinaz a, v, s i d v reguljacii sokratimosti kardiomiocitov (obzor. Soobshhenie II). Zhurnal mediko-biologicheskih issledovanij. 2015; 3: 55–65 (in Russian)]
- Ao H., Liu B., Li H., Lu L. Egr1 mediates retinal vascular dysfunction in diabetes mellitus via promoting p53 transcription. J. Cell Mol. Med. 2019; 23 (5): 3345–56. doi: 10.1111/jcmm.14225
- Karege F., Perroud N., Schürhoff F., Méary A., Marillier G., Burkhardt S., Ballmann E., Fernandez R., Jamain S., Leboyer M., La Harpe R., Malafosse A. Association of AKT1 gene variants and protein expression in both schizophrenia and bipolar disorder. Genes Brain Behav. 2010; 9 (5): 503–11. doi: 10.1111/j.1601-183X.2010.00578.x
- Huang X., Liu G., Guo J., Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int. J. Biol. Sci. 2018; 14 (11): 1483–96. doi: 10.7150/ijbs.27173
- Lee M.Y., Luciano A.K., Ackah E., Rodriguez-Vita J., Bancroft T.A., Eichmann A., Simons M., Kyriakides T.R., Morales-Ruiz M., Sessa W.C. Endothelial Akt1 mediates angiogenesis by phosphorylating multiple angiogenic substrates. Proc Natl Acad Sci USA. 2014; 111 (35): 12865–70. doi: 10.1073/pnas.1408472111
- Zhang M., Yang J., Zhao X., Zhao Y., Zhu S. Network pharmacology and molecular docking study on the active ingredients of qidengmingmu capsule for the treatment of diabetic retinopathy. Sci Rep. 2021; 11 (1): 7382. doi: 10.1038/s41598-021-86914-8
- Costanzo M.C., von Grotthuss M., Massung J., Jang D., Caulkins L., Koesterer R., Gilbert C., Welch R.P., Kudtarkar P., Hoang Q., Boughton A.P., Singh P., Sun Y., Duby M., Moriondo A., Nguyen T., Smadbeck P., Alexander B.R., Brandes M., Carmichael M., Dornbos P., Green T., Huellas-Bruskiewicz K.C., Ji Y., Kluge A., McMahon A.C., Mercader J.M., Ruebenacker O., Sengupta S., Spalding D., Taliun D. AMP-T2D Consortium. Smith P., Thomas M.K., Akolkar B., Brosnan M.J., Cherkas A., Chu A.Y., Fauman E.B., Fox C.S., Kamphaus T.N., Miller M.R., Nguyen L., Parsa A., Reilly D.F., Ruetten H., Wholley D., Zaghloul N.A., Abecasis G.R., Altshuler D., Keane T.M., McCarthy M.I., Gaulton K.J., Florez J.C., Boehnke M., Burtt N.P., Flannick J. The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits. Cell Metab. 2023; 35 (4): 695–710.e6. doi: 10.1016/j.cmet.2023.03.001
- Sun Y., Gao C., Liu H., Liu X., Yue T. Exploring the mechanism by which aqueous Gynura divaricata inhibits diabetic foot based on network pharmacology, molecular docking and experimental verification. Mol. Med. 2023; 29 (1): 11. doi: 10.1186/s10020-023-00605-w. PMID: 36670362
- Zhao J., Zeng Z. Combined effects of AKT serine/threonine kinase 1 polymorphisms and environment on congenital heart disease risk: A case-control study. Medicine (Baltimore). 2020; 99 (26): e20400. doi: 10.1097/MD.0000000000020400
- Millischer V., Matheson G.J., Martinsson L., Römer Ek I., Schalling M., Lavebratt C., Backlund L. AKT1 and genetic vulnerability to bipolar disorder. Psychiatry Res. 2020; 284: 112677. doi: 10.1016/j.psychres.2019.
- Maruei-Milan R., Saravani M., Heidari Z., Asadi-Tarani M., Salimi S. Effects of the MTOR and AKT1 genes polymorphisms on papillary thyroid cancer development. IUBMB Life. 2020; 72 (12): 2601–10. doi: 10.1002/iub.238
- Li Y., Zhu L., Yao H., Zhang Y., Kong X., Chen L., Song Y., Mu A., Li X. Association of Inflammation-Related Gene Polymorphisms With Susceptibility and Radiotherapy Sensitivity in Head and Neck Squamous Cell Carcinoma Patients in Northeast China. Front Oncol. 2021; 11: 651632. doi: 10.3389/fonc.2021.651632
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