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Do GSTM1 and GSTT1 polymorphisms influence the risk of developing mitochondrial diseases in a Tunisian population?

Ghorbel, Raouia; Ben Salah, Ghada; Ghorbel, Rania; Ben Mahmoud, Afif; Chamkha, Imen LU ; Mkaouar-Rebai, Emna; Ammar-Keskes, Leila and Fakhfakh, Faiza (2017) In Environmental Science and Pollution Research
Abstract

Mitochondria play an essential role to supply the cell with metabolic energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As a consequence, they are also the primary source of cellular reactive oxygen species (ROS) which can cause oxidative damage of individual respiratory chain complexes. Indeed, affected OXPHOS subunits result in decreases in ATP production and increases in ROS formation which generate oxidative phosphorylation deficiency leading to mitochondrial dysfunctions. It has been suggested that ROS play a vital role in the pathogenesis of mitochondrial diseases. To the best of our knowledge, this is the first study which aimed to investigate the genetic variant effect of the... (More)

Mitochondria play an essential role to supply the cell with metabolic energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As a consequence, they are also the primary source of cellular reactive oxygen species (ROS) which can cause oxidative damage of individual respiratory chain complexes. Indeed, affected OXPHOS subunits result in decreases in ATP production and increases in ROS formation which generate oxidative phosphorylation deficiency leading to mitochondrial dysfunctions. It has been suggested that ROS play a vital role in the pathogenesis of mitochondrial diseases. To the best of our knowledge, this is the first study which aimed to investigate the genetic variant effect of the antioxidant enzymes GSTM1 and GSTT1 on mitochondrial disease among a Tunisian population. In this report, 109 patients with mitochondrial disease and 154 healthy controls were genotyped by multiplex PCR amplification, and data were analyzed by SPSS v20 software. The results showed that GSTM1 null genotype was found to be associated with mitochondrial disease with a protective effect; however, no significant association of GSTT1 polymorphism with mitochondrial disease risk was revealed. But, interestingly, our findings highlight that GSTM1 active and GSTT1 null genotype combination increased by three fold the risk of developing mitochondrial disease with pc = 0.020, notably mitochondrial myopathy with pc = 0.046 and Leigh syndrome with pc = 0.042. In conclusion, this study suggests that GSTM1 active and GSTT1 null genotype combination might be a risk factor in developing mitochondrial disease.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Gene polymorphism, Glutathione S-transferases (GSTs), GSTM1, GSTT1, Mitochondrial disease, Oxidative stress
in
Environmental Science and Pollution Research
pages
9 pages
publisher
Springer
external identifiers
  • scopus:85037732438
ISSN
0944-1344
DOI
10.1007/s11356-017-0775-7
language
English
LU publication?
yes
id
fa0bb900-0049-42bb-92fb-1771dc8f311f
date added to LUP
2018-01-03 12:51:23
date last changed
2018-01-04 03:00:02
@article{fa0bb900-0049-42bb-92fb-1771dc8f311f,
  abstract     = {<p>Mitochondria play an essential role to supply the cell with metabolic energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As a consequence, they are also the primary source of cellular reactive oxygen species (ROS) which can cause oxidative damage of individual respiratory chain complexes. Indeed, affected OXPHOS subunits result in decreases in ATP production and increases in ROS formation which generate oxidative phosphorylation deficiency leading to mitochondrial dysfunctions. It has been suggested that ROS play a vital role in the pathogenesis of mitochondrial diseases. To the best of our knowledge, this is the first study which aimed to investigate the genetic variant effect of the antioxidant enzymes GSTM1 and GSTT1 on mitochondrial disease among a Tunisian population. In this report, 109 patients with mitochondrial disease and 154 healthy controls were genotyped by multiplex PCR amplification, and data were analyzed by SPSS v20 software. The results showed that GSTM1 null genotype was found to be associated with mitochondrial disease with a protective effect; however, no significant association of GSTT1 polymorphism with mitochondrial disease risk was revealed. But, interestingly, our findings highlight that GSTM1 active and GSTT1 null genotype combination increased by three fold the risk of developing mitochondrial disease with p<sub>c</sub> = 0.020, notably mitochondrial myopathy with p<sub>c</sub> = 0.046 and Leigh syndrome with p<sub>c</sub> = 0.042. In conclusion, this study suggests that GSTM1 active and GSTT1 null genotype combination might be a risk factor in developing mitochondrial disease.</p>},
  author       = {Ghorbel, Raouia and Ben Salah, Ghada and Ghorbel, Rania and Ben Mahmoud, Afif and Chamkha, Imen and Mkaouar-Rebai, Emna and Ammar-Keskes, Leila and Fakhfakh, Faiza},
  issn         = {0944-1344},
  keyword      = {Gene polymorphism,Glutathione S-transferases (GSTs),GSTM1,GSTT1,Mitochondrial disease,Oxidative stress},
  language     = {eng},
  month        = {12},
  pages        = {9},
  publisher    = {Springer},
  series       = {Environmental Science and Pollution Research},
  title        = {Do GSTM1 and GSTT1 polymorphisms influence the risk of developing mitochondrial diseases in a Tunisian population?},
  url          = {http://dx.doi.org/10.1007/s11356-017-0775-7},
  year         = {2017},
}