The role of GSTM1 and GSTT1 deletion variants and alcohol consumption profile in the development of alcoholic liver cirrhosis

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Abstract
Introduction/Objective. Alcoholic liver cirrhosis (ALC) is the primary cause of alcohol abuse-related mortality, resulting from alcohol-induced oxidative stress. Glutathione S-transferases (GSTM1, GSTT1) are enzymes essential for detoxification, and their deficiency may contribute to the onset of chronic inflammation and disease progression. This study sought to investigate the relationship between GSTM1 and GSTT1 deletions and ALC, as well as alcohol consumption patterns in cirrhosis development. Methods. The analysis included 114 ALC patients and 262 controls, with GSTM1 and GSTT1 deletions assessed via multiplex PCR. Results. Findings indicated that individuals with the GSTM1 null genotype had a three-fold increased risk of developing ALC (95% CI, 1.87–4.81; p < 0.0001), whereas GSTT1 null genotypes showed no significant impact. Individuals with both GSTM1 null and GSTT1 null genotypes exhibited an 11-fold heightened risk of ALC (OR = 11.21, 95% CI = 3.30–38.14, p < 0.001). Furthermore, patients who commenced alcohol consumption at 22.5 years or older developed cirrhosis more rapidly than their younger counterparts (p < 0.001). Conclusion. GSTM1 null and combined GSTM1/GSTT1 null genotypes constitute significant risk factors for ALC, with patients who started drinking at an older age experiencing accelerated disease progression irrespective of alcohol intake levels.
Funding Information
  • Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja (451-03-66/2024-03/200042)

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