¹Department of Molecular Biology and Genomic Medicine from CUCS, University of Guadalajara, Jalisco.

²Intituto de Nutrición, University de la Sierra Sur, SUNEO, Oaxaca, México.

³Departamento of physiology, from CUCS, University of Guadalajara, Jalisco.

⁴OPD Hospital Civil de Guadalajara Fray Antonio Alcalde.

⁵CA-Emprendedores, Universidad Autónoma Benito Juárez de Oaxaca.

⁶Department of Public Health from University of Guadalajara, Jalisco México.

Corresponding Author: Sergio Alberto Ramirez-Garcia, Intituto de Nutrición, University de la Sierra Sur, SUNEO, Oaxaca, México, E-Mail: [email protected]

Received Date: 02 Nov 2018   Accepted Date: 08 Nov 2018   Published Date: 12 Nov 2018

Copyright ©2018 Ramirez-Garcia SAR

Citation: Madrigal-Ruiz PM, Ramirez-Garcia SAR, FloresAlvarado LJ, Madrigal-Ruiz DA, et al. (2018). Atm is a Gene Target in the Clinical Following of Diabetic Retinopathy.Mathews J Ophthalmol 3(1): 022.

INTRODUCTION

In the current era of translational medicine, it is important to search for genetic markers that may be useful in the clinical management of patients with diabetic retinopathy, as well as for their prognosis and evolution, one of the genes worth exploring in this regard, is the ataxia telangiectasia gene known as ATM. This gene may be the connection between genomic instability and metabolic stress that occurs in diabetic patients.

The ATM gene has its locus on chromosome 11q23, has 66 exons and codes for the ATM protein, which is a regulator of the cell cycle through the phosphorylation of TP53, BCRA-1, BLM, NBS-1, CHK2, CDK2, CD25, FANDC, RAD 17. The ATM protein, has five domains, one of the most important is the N-terminal region encoded by the 3 ‘portion of the gene because it shows homology with the mammalian and mouse IPK3. This is relevant since it regulates AMPK, which regulates and amplifies metabolism, participating in the regulation of insulin signaling, hence it is also a hepatic genomic marker of metformin, since it is used in the treatment of diabetes and as adjuvant in cancer and is related to dysglycemia and insulin resistance [1-13].

The genetic variants of ATM at the level of polymorphisms have been associated with the risk of diabetes in the Asian population, as in the case of the SNP rs189037C>T with locus in the promoter region, while the SNP rs11212617 has been associated with the response to metformin in Iranian population and population in the United Kingdom, as well as the development of coronary syndromes. Effectively functional SNP rs189037 participates in coronary stenosis. Increased expression of the ATM gene in diabetics and in patients with coronary syndromes has been reported at the expression level [1-13].

With these considerations we can comment insights of the ATM gene, which is a regulator of the metabolism of glucose control, its alteration leads to dysglycemia and insulin resistance, at the level of ophthalmology this is very important because the alteration of the homeostasis of the glucose leads to the development of retinopathy in the diabetic patient or to the progression of retinopathy, this is a frontier of research that has to be explored both by association studies with polymorphisms such as SNP rs189037 and rs11212617 as well as expression level genetics. There is evidence that can explain why we make this application; since ATM acts as a defense against a variety of stressors, at least demonstrated at the level of hematopoietic stem cells (HSC) of the bone marrow (BM). The loss or dysfunction of ATM is detrimental both to the function of HSC and to microvascular repair, whose chronicity in diabetics represents a condition associated with HSC depletion and inadequate vascular repair, in rodent and microarray models in individuals diabetics, show an increase of ATM mRNA. Second, some ATM null alleles have been found in idiopathic perifoveal telangiectasia [1-13].

Undoubtedly, these evidences suggest that the ATM gene is the connection between genomic instability, as well as the cell cycle and metabolic stress that occurs in diabetic patients, which can lead to the development of chronic microangiopathic complications such as diabetic retinopathy. , which will have to be demonstrated in the coming years.

REFERENCES

1. Ding X, Hao Q, Yang M, Chen T, et al. (2017). Polymorphism rs189037C > T in the promoter region of the ATM gene may associate with reduced risk of T2DM in older adults in China: a case control study. BMC Med Genet. 18(1): 84.
2. Luizon MR, Eckalbar WL, Wang Y, Jones SL, et al. (2016). Genomic Characterization of Metformin Hepatic Response. PLoS Genet. 12(11): e1006449.
3. Shokri F, Ghaedi H, Ghafouri Fard S, Movafagh A , et al. (2016). Impact of ATM and SLC22A1 Polymorphisms on Therapeutic Response to Metformin in Iranian Diabetic Patients. Int J Mol Cell Med. 5(1): 1-7.
4. Connelly PJ, Smith N, Chadwick R, Exley AR et al. (2016). Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance. Diabet Med. 33(3): 371-375.
5. Bhatwadekar AD, Duan Y, Chakravarthy H, Korah M, et al. (2016). Ataxia Telangiectasia Mutated Dysregulation Results in Diabetic Retinopathy. Stem Cells. 34(2): 405-417.
6. Ahmadi A, Behmanesh M, Boroumand MA, Tavallaei M, et al. (2015). Up-regulation of MSH2, XRCC1 and ATM genes in patients with type 2 diabetes and coronary artery disease. Diabetes Res Clin Pract. 109(3): 500-506.
7. Vilvanathan S, Gurusamy U, Mukta V, Das AK, et al. (2014). Allele and genotype frequency of a genetic variant in ataxia telangiectasia mutated gene affecting glycemic response to metformin in South Indian population. Indian J Endocrinol Metab. 18(6): 850-854.
8. Schiekofer S, Bobak I, Kleber ME, Maerz Wet, al. (2014). Association between a gene variant near ataxia telangiectasia mutated and coronary artery disease in men. Diab Vasc Dis Res. 11(1): 60-63.
9. Mannino GC and Sesti G. (2012). Individualized therapy for type 2 diabetes: clinical implications of pharmacogenetic data. Mol Diagn Ther. 16(5): 285-302.
10. van Leeuwen N, Nijpels G, Becker ML, Deshmukh H, et al. (2012). A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts. Diabetologia. 55(7): 1971-1977.
11. Li S, Zhang L, Chen T, Tian B, et al. (2011). Functional polymorphism rs189037 in the promoter region of ATM gene is associated with angiographically characterized coronary stenosis. Atherosclerosis. 219(2): 694-697
12. Go DARTS and UKPDS Diabetes Pharmacogenetics Study Group, Wellcome Trust Case Control Consortium, Zhou K, Bellenguez C, et al. (2011). Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet. 43(2): 117-120.
13. Barbazetto IA, Room M, Yannuzzi NA, Barile GR, et al. (2008). ATM gene variants in patients with idiopathic perifoveal telangiectasia. Invest Ophthalmol Vis Sci. 49(9): 3806-3811.