open access

Vol 9, No 3 (2020)
ORIGINAL ARTICLES
Published online: 2020-06-01
Get Citation

Molecular genetic analysis of leucine tRNA in relevance to type 2 diabetes mellitus

Niaz Muhammad Khan, Hayat Ullah, Abdur Raziq, Adnan Ali Khan, Muhammad Waseem Khan
DOI: 10.5603/DK.2020.0018
·
Clinical Diabetology 2020;9(3):167-173.

open access

Vol 9, No 3 (2020)
ORIGINAL ARTICLES
Published online: 2020-06-01

Abstract

Background. Several point mutations in the mitochondrial DNA cause maternally inherited metabolic disorders. The most common type of mutation A3243G in the gene of transfer RNA leucine (tRNALeu(UUR)) is thought to be responsible for the prevalence of type 2 diabetes mellitus. This study was designed to analyze the tRNALeu(UUR) gene of mtDNA of the diabetic individuals with familial history of diabetes to identify the point mutations A3243G.

Material and methods. Saliva samples were preferred as a source of DNA to minimize the risk of infection. DNA was successfully extracted from their saliva. Samples of high-quality DNA was amplified with PCR and sequenced in Macrogen Inc. Korea.

Results. The m.3243A>G mutation in mitochondrial tRNALeu(UUR) gene was not observed.

Conclusion. The result shows that the m.3243A>G mutation in mitochondrial tRNALeu(UUR) gene is not frequent cause of type 2 and some other factors may be possible i.e. genetic, behavioral or environmental. It is recommended that the sample size for diabetic individuals need to be increased for a future study and screened for the mitochondrial as well as other mutations of nuclear origin.

Abstract

Background. Several point mutations in the mitochondrial DNA cause maternally inherited metabolic disorders. The most common type of mutation A3243G in the gene of transfer RNA leucine (tRNALeu(UUR)) is thought to be responsible for the prevalence of type 2 diabetes mellitus. This study was designed to analyze the tRNALeu(UUR) gene of mtDNA of the diabetic individuals with familial history of diabetes to identify the point mutations A3243G.

Material and methods. Saliva samples were preferred as a source of DNA to minimize the risk of infection. DNA was successfully extracted from their saliva. Samples of high-quality DNA was amplified with PCR and sequenced in Macrogen Inc. Korea.

Results. The m.3243A>G mutation in mitochondrial tRNALeu(UUR) gene was not observed.

Conclusion. The result shows that the m.3243A>G mutation in mitochondrial tRNALeu(UUR) gene is not frequent cause of type 2 and some other factors may be possible i.e. genetic, behavioral or environmental. It is recommended that the sample size for diabetic individuals need to be increased for a future study and screened for the mitochondrial as well as other mutations of nuclear origin.

Get Citation

Keywords

diabetes mellitus, leucine tRNA, mitochondrial DNA, point mutation

About this article
Title

Molecular genetic analysis of leucine tRNA in relevance to type 2 diabetes mellitus

Journal

Clinical Diabetology

Issue

Vol 9, No 3 (2020)

Pages

167-173

Published online

2020-06-01

DOI

10.5603/DK.2020.0018

Bibliographic record

Clinical Diabetology 2020;9(3):167-173.

Keywords

diabetes mellitus
leucine tRNA
mitochondrial DNA
point mutation

Authors

Niaz Muhammad Khan
Hayat Ullah
Abdur Raziq
Adnan Ali Khan
Muhammad Waseem Khan

References (34)
  1. Naveed A, Wahid M, Naveed A. Mitochondrial tRNALeu(UUR) gene mutation and maternally inherited diabetes mellitus in Pakistani population. Int J Diabetes Mellit. 2009; 1(1): 11–15.
  2. Greiner S, Sobanski J, Bock R. Why are most organelle genomes transmitted maternally? BioEssays. 2014; 37(1): 80–94.
  3. Wang M, Zhou XL, Liu RJ, et al. Multilevel functional and structural defects induced by two pathogenic mitochondrial tRNA mutations. Biochem J. 2013; 453(3): 455–465.
  4. Li R, Guan MX. Human mitochondrial leucyl-trna synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes. Mol Cell Biol. 2010; 30(9): 2147–2154.
  5. Guery B. The spectrum of systemic involvement in adults presenting with renal lesion and mitochondrial tRNA(Leu) gene mutation. Journal of the American Society of Nephrology. 2003; 14(8): 2099–2108.
  6. Schon E, DiMauro S, Hirano M. Human mitochondrial DNA: roles of inherited and somatic mutations. Nat Rev Genet. 2012; 13(12): 878–890.
  7. Brandle M, Lehmann R, Maly FE, et al. Diminished insulin secretory response to glucose but normal insulin and glucagon secretory responses to arginine in a family with maternally inherited diabetes and deafness caused by mitochondrial tRNALEU(UUR) gene mutation. Diabetes Care. 2001; 24(7): 1253–1258.
  8. Gerbitz KD, Gempel K, Brdiczka D. Mitochondria and diabetes: genetic, biochemical, and clinical implications of the cellular energy circuit. Diabetes. 1996; 45(2): 113–126.
  9. Nile D, Brown A, Kumaheri M, et al. Age-Related mitochondrial DNA depletion and the impact on pancreatic beta cell function. PLoS ONE. 2014; 9(12): e115433.
  10. Schaefer A, Walker M, Turnbull D, et al. Endocrine disorders in mitochondrial disease. Mol Cell Endocrinol. 2013; 379(1-2): 2–11.
  11. Hart LM't, Hansen T, Rietveld I, et al. Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene. Diabetes. 2005; 54(6): 1892–1895.
  12. Park H, Davidson E, King M. The pathogenic A3243G mutation in human mitochondrial tRNALeu(UUR) decreases the efficiency of aminoacylation†. Biochemistry. 2003; 42(4): 958–964.
  13. Aidar M, Line S. A simple and cost-effective protocol for DNA isolation from buccal epithelial cells. Braz Dent J. 2007; 18(2): 148–152.
  14. Latif A, Ghafoor A, Wali A, et al. Did diabetes mellitus affect treatment outcome in drug-resistant tuberculosis patients in Pakistan from 2010 to 2014? Public Health Action. 2018; 8(1): 14–19.
  15. Reinehr T. Type 2 diabetes mellitus in children and adolescents. World J Diabetes. 2013; 4(6): 270–281.
  16. Razaq S, Khan MW, Masood Z, et al. et al.. An investigation on the prevalance of gestational diabetes mellitus in the pregnant women of province balochistan. WJMS. 2015; 12(2): 198–203.
  17. Brown LC, Majumdar SR, Newman SC, et al. History of depression increases risk of type 2 diabetes in younger adults. Diabetes Care. 2005; 28(5): 1063–1067.
  18. Wahid M, Naveed AK, Hussain I. Insulin and glucagon ratio in the pathophysiology of diabetic ketoacidosis and hyperosmolar hyperglycemic non-ketotic diabetes. J Coll Physicians Surg Pak. 2006; 16(1): 11–14.
  19. Lorenzoni P, Werneck L, Kay C, et al. When should MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) be the diagnosis? Arquivos de Neuro-Psiquiatria. 2015; 73(11): 959–967.
  20. Jiang Z, Wu X, Zhu Y. Variant at position 10,055 in mitochondrial tRNAGly gene has a negative association with aplastic anemia. Mitochondrial DNA Part A. 2015; 27(5): 3086–3088.
  21. Martikainen M, Rönnemaa T, Majamaa K. Prevalence of mitochondrial diabetes in southwestern Finland: a molecular epidemiological study. Acta Diabet. 2012; 50(5): 737–741.
  22. Wang S, Wu S, Zheng T, et al. Mitochondrial DNA mutations in diabetes mellitus patients in Chinese Han population. Gene. 2013; 531(2): 472–475.
  23. Abrar S, Muhammad K, Zaman H, et al. Molecular genetic analysis of Type II diabetes associated m.3243A>G mitochondrial DNA mutation in a Pakistani family. Egyptian Journal of Medical Human Genetics. 2017; 18(3): 305–308.
  24. Zambelli A, Vidal-Rioja L. Lack of association between mitochondrial DNA mutation np3243 and maternally inherited diabetes mellitus. Clinical Biochemistry. 1999; 32(1): 81–82.
  25. Rusanen H, Majamaa K, Tolonen U, et al. Demyelinating polyneuropathy in a patient with the tRNALeu(uur) mutation at base pair 3243 of the mitochondrial DNA. Neurology. 1995; 45(6): 1188–1192.
  26. Mohan V, Radha V, Nguyen T, et al. Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India. BMC Med Genet. 2018; 19(1): 22.
  27. Malecki M, Klupa T, Wanic K, et al. Search for mitochondrial A3243G tRNALeu mutation in Polish patients with type 2 diabetes mellitus. Med Sci Monit. 2001; 7(2): 246-250; PMID: 421154.
  28. Kuzuya T, Matsuda A. Classification of diabetes on the basis of etiologies versus degree of insulin deficiency. Diabetes Care. 1997; 20(2): 219–220.
  29. Lehto M, Tuomi T, Mahtani MM, et al. Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect. J Clin Invest. 1997; 99(4): 582–591.
  30. Guerra C, Navarro P, Valverde A, et al. Brown adipose tissue–specific insulin receptor knockout shows diabetic phenotype without insulin resistance. J Clin Invest. 2001; 108(8): 1205–1213.
  31. Bhirud P. BalasahebBJ. Conceptual study of malnutrition related diabetes mellitus. JAIMS. 2019; 4(1): 89–95.
  32. Rötig A, Cormier V, Chatelain P, et al. Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300). J Clin Invest. 1993; 91(3): 1095–1098.
  33. Schober E, Rami B, Grabert M, et al. Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database. Diabet Med. 2009; 26(5): 466–473.
  34. Catchpole B, Kennedy LJ, Davison LJ, et al. Canine diabetes mellitus: from phenotype to genotype. J Small Anim Pract. 2008; 49(1): 4–10.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

 

Wydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl