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Current Psychiatry Research and Reviews

Editor-in-Chief

ISSN (Print): 2666-0822
ISSN (Online): 2666-0830

Research Article

Glutathione S Transferase Theta1 and Mu1 (GSTT1 and GSTM1) Deletion Among Autistic Population of India

Author(s): Rajat Hegde*, Smita Hegde, Suyamindra S. Kulkarni, Kusal K. Das and Pramod B. Gai*

Volume 20, Issue 2, 2024

Published on: 04 April, 2023

Page: [152 - 161] Pages: 10

DOI: 10.2174/2666082219666230302142608

Price: $65

Abstract

Introduction: Oxidative stress is an imbalance between an organism's reactive oxygen species (ROS) production and antioxidant defence capacity. Long-term oxidative stress contributes to cellular ageing and plays a role in the pathogenesis of several diseases. Several investigations indicated that oxidative stress has a role in the pathogenesis of ASD.

Objectives: Present study was undertaken to record the association of GSTTT1 and GSTM1 null genotype among the autistic population of India.

Methods: Genomic DNA was isolated from 108 autistic children along with healthy agematched control. The quality and quantity of the isolated genomic DNA were analysed. GSTT1 and GSTM1 null genotype was analysed using polymerase chain reaction with internal positive control. Statistical analysis was performed using SPSS 15.0.

Results: Present study included 85 males and 23 females with a mean age of 11.7 ± 3.5 and 75 males and 33 females with a mean age of 11 ± 2.0 in the control group. 32 (29.6%) autistic cases showed null genotypes for GSTT1 and 21(19.4%) autistic children showed null genotypes for GSTM1. 3 (2.85%) control children showed a null genotype for GSTT1 and 5 (4.6%) control children showed a null genotype for GSTM1. The GSTT1 and GSTM1 null genotypes were observed to be significantly associated with the risk of autism (p value-0.0001, OR-14.73, 95% CI 4.35-49.90) and (p value-0.003, OR-4.731, 95% CI 1.71-13.08) respectively.

Conclusion: The findings of our study suggested that GSTT1 and GSTM1 null genotype is one of the potential risk factors for autism through oxidative stress mechanism in our population.

[1]
Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 2015; 97: 55-74.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.040] [PMID: 25942353]
[2]
Barbosa KBF, Costa NMB, Alfenas RCG, Paula SO, Minim VPR, Bressan J. Oxidative stress: Concept, implications and modulatory factors. J Nutr 2010; 23(4): 629-43.
[3]
Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J 2012; 5(1): 9-19.
[http://dx.doi.org/10.1097/WOX.0b013e3182439613] [PMID: 23268465]
[4]
McCord JM. The evolution of free radicals and oxidative stress. Am J Med 2000; 108(8): 652-9.
[http://dx.doi.org/10.1016/S0002-9343(00)00412-5] [PMID: 10856414]
[5]
Halliwell B. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol 2006; 141(2): 312-22.
[http://dx.doi.org/10.1104/pp.106.077073] [PMID: 16760481]
[6]
Matsui A, Ikeda T, Enomoto K, et al. Increased formation of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, in human breast cancer tissue and its relationship to GSTP1 and COMT genotypes. Cancer Lett 2000; 151(1): 87-95.
[http://dx.doi.org/10.1016/S0304-3835(99)00424-3] [PMID: 10766427]
[7]
Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol 2001; 54(3): 176-86.
[http://dx.doi.org/10.1136/jcp.54.3.176] [PMID: 11253127]
[8]
Harman D. Role of free radicals in aging and disease. Ann N Y Acad Sci 1992; 673(1 Physiopatholo): 126-41.
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb27444.x] [PMID: 1485710]
[9]
Lee JD, Cai Q, Shu XO, Nechuta SJ. The role of biomarkers of oxidative stress in breast cancer risk and prognosis: A systematic review of the epidemiologic literature. J Womens Health (Larchmt) 2017; 26(5): 467-82.
[http://dx.doi.org/10.1089/jwh.2016.5973] [PMID: 28151039]
[10]
Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 2015; 6(3): 456-80.
[http://dx.doi.org/10.4239/wjd.v6.i3.456] [PMID: 25897356]
[11]
Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem 2006; 52(4): 601-23.
[http://dx.doi.org/10.1373/clinchem.2005.061408] [PMID: 16484333]
[12]
Rao AL, Bharani M, Pallavi V. Role of antioxidants and free radicals in health and disease. Adv Pharmacol Toxicol 2006; 7: 29-38.
[13]
Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010; 4(8): 118-26.
[http://dx.doi.org/10.4103/0973-7847.70902] [PMID: 22228951]
[14]
Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005; 45(1): 51-88.
[http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.095857] [PMID: 15822171]
[15]
Awasthi YC. Toxicology of glutathione transferases. CRC Press 2006.
[http://dx.doi.org/10.1201/9781420004489]
[16]
Barseem N, Elsamalehy M. Gene polymorphisms of glutathione S-Transferase T1/M1 in egyptian children and adolescents with type 1 diabetes mellitus. J Clin Res Pediatr Endocrinol 2017; 9(2): 138-43.
[http://dx.doi.org/10.4274/jcrpe.3690] [PMID: 27908841]
[17]
Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010; 107(9): 1058-70.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.223545] [PMID: 21030723]
[18]
Dandona P, Thusu K, Cook S, et al. Oxidative damage to DNA in diabetes mellitus. Lancet 1996; 347(8999): 444-5.
[http://dx.doi.org/10.1016/S0140-6736(96)90013-6] [PMID: 8618487]
[19]
Williams B, Gallacher B, Patel H, Orme C. Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro. Diabetes 1997; 46(9): 1497-503.
[http://dx.doi.org/10.2337/diab.46.9.1497] [PMID: 9287052]
[20]
Rizvi S, Raza ST, Mahdi F. Association of genetic variants with diabetic nephropathy. World J Diabetes 2014; 5(6): 809-16.
[http://dx.doi.org/10.4239/wjd.v5.i6.809] [PMID: 25512783]
[21]
Hegde R, Hegde S, Kulkarni SS, Pandurangi A, Gai PB, Das KK. Novel frameshift mutation in Indian autistic population causes neuroligin and neurexin binding defect. Gene Rep 2021; 24: 101245.
[http://dx.doi.org/10.1016/j.genrep.2021.101245]
[22]
Chen JA, Peñagarikano O, Belgard TG, Swarup V, Geschwind DH. The emerging picture of autism spectrum disorder: genetics and pathology. Annu Rev Pathol 2015; 10(1): 111-44.
[http://dx.doi.org/10.1146/annurev-pathol-012414-040405] [PMID: 25621659]
[23]
Raina SK, Chander V, Bhardwaj AK, et al. Prevalence of autism spectrum disorder among rural, urban, and tribal children (1-10 years of age). J Neurosci Rural Pract 2017; 8(3): 368-74.
[http://dx.doi.org/10.4103/jnrp.jnrp_329_16] [PMID: 28694615]
[24]
Moon SJ, Hwang JS, Shin AL, et al. Accuracy of the Childhood Autism Rating Scale: a systematic review and meta-analysis. Dev Med Child Neurol 2019; 61(9): 1030-8.
[http://dx.doi.org/10.1111/dmcn.14246] [PMID: 30977125]
[25]
Sandin S, Schendel D, Magnusson P, et al. Autism risk associated with parental age and with increasing difference in age between the parents. Mol Psychiatry 2016; 21(5): 693-700.
[http://dx.doi.org/10.1038/mp.2015.70] [PMID: 26055426]
[26]
Ravi S, Chandrasekaran V, Kattimani S, Subramanian M. Maternal and birth risk factors for children screening positive for autism spectrum disorders on M-CHAT-R. Asian J Psychiatr 2016; 22: 17-21.
[http://dx.doi.org/10.1016/j.ajp.2016.04.001] [PMID: 27520889]
[27]
Mamidala MP, Kalikiri MK, Praveen Kumar PTV, Rajesh N, Vallamkonda OR, Rajesh V. Consanguinity in India and its association with autism spectrum disorder. Autism Res 2015; 8(2): 224-8.
[http://dx.doi.org/10.1002/aur.1431] [PMID: 25428403]
[28]
Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology 2006; 13(3): 171-81.
[http://dx.doi.org/10.1016/j.pathophys.2006.05.007] [PMID: 16766163]
[29]
Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: Current state. Nutr J 2015; 15(1): 71.
[http://dx.doi.org/10.1186/s12937-016-0186-5] [PMID: 27456681]
[30]
Rose S, Melnyk S, Pavliv O, et al. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2012; 2(7): e134.
[http://dx.doi.org/10.1038/tp.2012.61] [PMID: 22781167]
[31]
Oshodi Y, Ojewunmi O, Oshodi TA, et al. Oxidative stress markers and genetic polymorphisms of glutathione S-transferase T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos, Nigeria. Niger J Clin Pract 2017; 20(9): 1161-7.
[http://dx.doi.org/10.4103/njcp.njcp_282_16] [PMID: 29072241]
[32]
Said S, Moubarz G, Awadalla H, et al. Role of glutathione- s-transferase M1 (GSTM1) and T1 (GSTT1) genes on aluminum concentration and oxidative markers among autistic children. Egypt J Chem 2021; 0(0): 0.
[http://dx.doi.org/10.21608/ejchem.2021.94656.4464]
[33]
Bjørklund G, Meguid NA, El-Bana MA, et al. Oxidative stress in autism spectrum disorder. Mol Neurobiol 2020; 57(5): 2314-32.
[http://dx.doi.org/10.1007/s12035-019-01742-2] [PMID: 32026227]
[34]
Rahbar MH, Samms-Vaughan M, Ma J, et al. Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders. Res Autism Spectr Disord 2015; 12: 1-9.
[http://dx.doi.org/10.1016/j.rasd.2014.12.008] [PMID: 25685181]
[35]
Taioli E, Flores-Obando RE, Agalliu I, et al. Multi-institutional prostate cancer study of genetic susceptibility in populations of African descent. Carcinogenesis 2011; 32(9): 1361-5.
[http://dx.doi.org/10.1093/carcin/bgr119] [PMID: 21705483]
[36]
Chen CL, Liu Q, Relling MV. Simultaneous characterization of glutathione S-transferase M1 and T1 polymorphisms by polymerase chain reaction in American whites and blacks. Pharmacogenetics 1996; 6(2): 187-91.
[http://dx.doi.org/10.1097/00008571-199604000-00005] [PMID: 9156696]
[37]
Li R, Boerwinkle E, Olshan AF, et al. Glutathione S-transferase genotype as a susceptibility factor in smoking-related coronary heart disease. Atherosclerosis 2000; 149(2): 451-62.
[http://dx.doi.org/10.1016/S0021-9150(99)00483-9] [PMID: 10729397]
[38]
Hiragi CO, Oliveira SF, Hatagima A, Ferreira LB, Grisolia CK, Klautau-Guimarães MN. Glutathione S-transferase M1 and T1 polymorphisms in Brazilian African descendants. Hum Biol 2007; 79(1): 131-40.
[http://dx.doi.org/10.1353/hub.2007.0025] [PMID: 17985662]
[39]
Saravana Devi S, Vinayagamoorthy N, Agrawal M, et al. Distribution of detoxifying genes polymorphism in Maharastrian population of central India. Chemosphere 2008; 70(10): 1835-9.
[http://dx.doi.org/10.1016/j.chemosphere.2007.08.008] [PMID: 17869325]
[40]
Buyske S, Williams TA, Mars AE, et al. Analysis of case-parent trios at a locus with a deletion allele: Association of GSTM1 with autism. BMC Genet 2006; 7(1): 8.
[http://dx.doi.org/10.1186/1471-2156-7-8] [PMID: 16472391]

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