Copy Number Variation in the and Genes and the Risk of Liver Cirrhosis in Eastern Ethiopia.

Background: Polymorphisms in glutathione S-transferase M1 () and T1 () can cause an entire gene deletion. The current methodology can accurately identify and copy number variants (CNVs), which may shed light on the true contribution of each gene copy to the cellular detoxification process and disease risk. Because liver cirrhosis is becoming a critical worldwide health issue, this study determined the CNVs of and and their relationship to the risk of liver cirrhosis.

Methods: In this study, we compared 106 patients with liver cirrhosis to 104 healthy controls. Real-time PCR was used to identify the CNVs of and . Logistic and linear regression models were used to estimate the relationship between liver cirrhosis and clinical chemistry variables with the CNVs, respectively.

Results: In 3.3% of the study participants, >2 copies of the or genes were detected. carriers had a significantly lower risk of liver cirrhosis (<0.05) compared with individuals who had homozygous deletion (adjusted odds ratio (AOR) = 0.47; 95% CI: 0.25, 0.86). This risk reduction was significant (<0.05) in patients with a single copy of the gene (AOR = 0.48; 95% CI: 0.25, 0.91). Those with ≥2 copies of combined and also had a significantly (<0.05) lower risk of developing liver cirrhosis compared with double null genotypes (AOR = 0.38; 95% CI: 0.16, 0.91, trend <0.001). Moreover, ≥2 copies of combined and genes were associated with a substantial decrease in alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels, respectively.

Conclusion: A single copy number of , and ≥2 copies of combined and genes were associated with a reduced risk of liver cirrhosis in Ethiopians. These findings underscore the importance of gene-environment interactions in the multifactorial development of liver cirrhosis.