Imbalanced oxidant and antioxidant ratio in myotonic dystrophy type 1

Abstract

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy affecting adults and is due to trinucleotide sequence (CTG) in the 3′ UTR region of DMPK gene located at 19q13.3 chromosome. The pathogenic mechanisms of multisystemic involvement of DM1 are still unclear. The increased levels of reactive oxygen species/free radicals and lipid peroxides and decreased antioxidant levels play an important role in the pathogenesis of DM1. Present study includes 20 DM1 patients and 40 age- and sex-matched controls. Malonilaldehyde (MDA), superoxide dismutase (SOD), glutathione peroxidise (GPX), glutathione-S-transferase (GST), reduced glutathione (GSH), and TAS levels were measured and its association with clinical phenotype were evaluated. Results revealed significantly higher levels of MDA (p = 0.002), SOD (p = 0.006), and TAS p = 0.004) and lower level of GPX (p = 0.003), GST (P < 0.001) and GSH (P = 0.016) in DM1 patients. A significant negative correlation of MDA level with dyspepsia and CK-MB and GST level with serum SCK, CK-MB, and diabetes were observed. However, a significant positive correlation of SOD level with serum CK-MB, CK-MM, and diabetes and negative correlation with facial weakness were noted. Though, GSH level had significant positive correlation with learning and writing disability, speech, and languages disability yet found negative correlation with duration of disease. The GPX and TAS showed no correlation with any clinical findings. Our data further support the pathogenic role of oxidative stress in DM1 of Indian origin and support the opportunity to undertake clinical trials with antioxidants in this disorder.

Keywords::

• myotonic dystrophy type 1
• oxidative stress
• reactive oxygen species
• lipid peroxidation
• antioxidant enzyme
• total antioxidant status

Acknowledgments

The authors are thankful to Sanjay Gandhi Post Graduate institute of Medical Sciences, Lucknow for providing infrastructure facility and Dr. Sunil Pradhan and Dr. Shubha R Phadke for referring patients. Ashok Kumar is thankful to DBT-New Delhi for his fellowship.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Ethics approval

The research has been approved by the Institutional Ethics Committee, SGPGIMS, Lucknow.