Significance of Single-Nucleotide Polymorphisms in mTOR (rs11204981) and ATG5 (rs510432) Genes in Allergic Diseases in Children

O.P. Volosovets, V.Ye. Dosenko, S.P. Kryvopustov, O.V. Pavlyk, O.V. Yeemets, D.O. Stroi


The objective of this study — to determine the association between single-nucleotide polymorphisms in mTOR (mammalian target of rapamycin) and ATG5 (autophagy related gene 5) genes and allergic phenotype in children. Genotyping for mTOR (rs11121704) and ATG5 (rs510432) was performed in group of patients with atopic diseases and in control group using real-time polymerase chain reaction. We have found that 50 (54.9 %) patients and 43 (49.4 %) healthy children had major allele (TT) of rs11121704 polymorphism; 36 (39.6 %) and 32 (36.8 %), respectively, had heterozygous allele (TC); 5 (5.5 %) and 12 (13.8 %) had minor allele (CC). Variants with CC genotype of rs11121704 in mTOR gene were revealed 2.5 times more frequently in the control group than among patients. Allelic variants in ATG5 gene were as follows: 51 (52 %) patients and 43 (44.3 %) healthy children had heterozygous allele (CT), 29 (29.6 %) and 21 (21.6 %), respectively, had minor allele (TT), and 18 (18.4 %) and 33 (34 %) had major allele (CC). TT genotype is associated with increased risk of early manifestation of bronchial asthma (until 3 years of life). We believe that polymorphisms in mTOR (rs11121704) and ATG5 (rs510432) genes may serve as important predictive markers in evaluating the risk of bronchial asthma and other allergic diseases in children.


single nucleotide polymorphism; autophagy; mTOR; ATG5; allergic diseases; children.


Brand E.B., Sivaprasad U. Th2 Cytokines and Atopic Dermatitis // J. Clin. Cell. Immunol. — 2011. — 2(3). — 110.

Cao Q., Ju X., Li P., Meng X., Shao P. et al. A functional variant in the MTOR promoter modulates its expression and is associated with renal cell cancer risk // PLoS One. — 2012. — 7(11). — e50302. doi: 10.1371/journal.pone.0050302.

Chen J., Shao P., Cao Q., Li P., Li J. et al. Genetic variations in a PTEN/AKT/mTOR axis and prostate cancer risk in a Chinese population // PLoS One. — 2012. — 7(7). — e40817. doi: 10.1371/journal.pone.0040817.

Datta S., Milner J.D. Rostrum. Altered T-cell receptor signaling in the pathogenesis of allergic disease // J. Allergy Clin. Immun. — 2011 — 127(2). — 351-354. Doi:10.1016/j.jaci.2010.11.0339.

Delgoffe G.M., Kole T.P., Zheng, Y., Zarek P.E., Matthews K.L., Xiao B., Worley P.F., Kozma S.C., Powell J.D. mTOR differentially regulates effector and regulatory T cell lineage commitment // Immunity. — 2009. — 30(6). — 832-844. doi: 10.1016/j.immuni.2009.04.014.

Delgoffe G.M., Pollizzi K.M., Waickman A.D., Heikamp E., Meyers D.J., Horton M.R., Bo Xiao, Worley P.F., Powell J.D. The mammalian Target of Rapamycin (mTOR) regulates T helper cell differentiation through the selective activation of mTORC1 and mTORC2 signaling // Nature immunology. — 2011. — 12(4). — 295-303.

Dunlop E.A., Tee A.R. mTOR and autophagy: A dynamic relationship governed by nutrients and energy // Semin. Cell. Dev. Biol. — 2014.

Fredriksson K., Fielhaber J.A., Lam J.K., Yao X., Meyer K.S. et al. Paradoxical Effects of Rapamycin on Experimental House Dust Mite-Induced Asthma // PLoS One. — 2012. — e33984. doi:10.1371/journal.pone.0033984.

He J., Wang M.Y., Qiu L.X., Zhu M.L., Shi T.Y. et al. Genetic variations of mTORC1 genes and risk of gastric cancer in an eastern chinese population // Mol. Carcinog. — 2013. — 52 Suppl. — 170-179. doi: 10.1002/mc.22013.

Hildebrandt M.A., Yang H., Hung M.C., Izzo J.G., Huang M. et al. Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy // J. Clin. Oncol. 2009. — 27. — 857-871. doi: 10.1200/jco.2008.17.6297.

Horvath I., Donnelly L.E., Kiss A. Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma // Am. J. Respir. Crit. Care Med. — 1998. — 158. — 1042-1046.

Huang L., Huang J., Wu P., Li Q., Rong L. et al. Association of genetic variations in mTOR with risk of childhood acute lymphoblastic leukemia in a Chinese population // Leuk. Lymphoma. — 2012. — 53. — 947-951. doi: 10.3109/10428194.2011.628062.

Jianbo Shao, Ying Li, Peiwei Zhao, Xin Yue, Xiaohui Liang Xuelian He. Association of mTOR Polymorphisms with Cancer Risk and Clinical Outcomes: A Meta-Analysis // PLoS One. — 2014 May 9. — 9(5). — e97085. DOI: 10.1371/journal.pone.0097085.

Jun A., Hiromichi H., Kazuyoshi K. Autophagy in the Pathogenesis of pulmonary disease // Intern. Med. — 2013. — 52. — 2295-2303.

Jyothula S.S., Eissa N.T. Autophagy and role in asthma // Curr. Opin. Pulm. Med. — 2013. — 19. — 30-35.

Martin L.J., Gupta J., Jyothula S.S. Functional variant in the autophagy-related gene 5 gene promoter is associated with childhood asthma // PLoS One. — 2012. — 7. — e33454.

O’Brien T.F., Xiao-Ping Zhong. The Role and Regulation of mTOR in T Lymphocyte Function // Arch. Immunol. Ther. Exp (Warsz). — 2012 Jun. — 60(3). — 173-181.

Poon A.H., Chouiali F., Tse S.M. Genetic and histologic evidence for autophagy in asthma pathogenesis // J. Allergy Clin. Immun. — 2012. — 129. — 569-571.

Pu X., Hildebrandt M.A., Lu C., Lin J., Stewart D.J. et al. PI3K/PTEN/AKT/mTOR pathway genetic variation predicts toxicity and distant progression in lung cancer patients receiving platinum-based chemotherapy // Lung. Cancer. — 2011. — 71. — 82-88. doi: 10.1016/j.lungcan.2010.04.008.

Shin J., Pan H. Xiao-Ping Zhong Regulation of mast cell survival and function by tuberous sclerosis complex 1 // Blood. — 2012 Apr 5. — 119(14). — 3306-3314.



  • There are currently no refbacks.

Copyright (c) 2016 CHILD`S HEALTH

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2018


 Яндекс.МетрикаSeo анализ сайта Рейтинг