Candidate Gene Polymorphisms Associated with Sarcopenia in HBV-, HCV-, and Alcohol-Related Liver Cirrhosis: CYP2C9, SOD2, and TGFβ1 in an Uzbek Cohort

Abstract

Background: Sarcopenia is a frequent complication of liver cirrhosis, but the contribution of host genetic variability to muscle loss remains insufficiently characterized. This study evaluated candidate polymorphisms in CYP2C9, SOD2, and TGFβ1 in patients with cirrhosis of different etiologies, stratified by sarcopenia status.

Methods: A candidate-gene analysis was performed within a cohort of patients with HBV-, HCV-, and alcohol-related liver cirrhosis. According to the molecular-genetic tables in the dissertation, the analyzed subgroups comprised HBV cirrhosis with/without sarcopenia (n=40/60), HCV cirrhosis with/without sarcopenia (n=40/60), alcohol-related cirrhosis with/without sarcopenia (n=20/40), and healthy controls (n=40). Peripheral-blood DNA was isolated and polymorphisms were assessed by PCR-based methods. The investigated variants were CYP2C9 Ile359Leu, CYP2C9 Arg144Cys, SOD2 Ala16Val, and TGFβ1 Arg25Pro.

Results: Risk-allele enrichment was observed consistently in sarcopenic patients. The CYP2C9 Leu allele occurred in 30.0%, 33.8%, and 40.0% of sarcopenic HBV, HCV, and alcohol-related cirrhosis groups versus 12.5%, 15.0%, and 13.8% in the corresponding non-sarcopenic groups. The SOD2 Val allele occurred in 85.0%, 80.0%, and 85.0% versus 58.3%, 60.0%, and 65.0%, respectively. The TGFβ1 Pro allele showed the largest separation: 57.5%, 60.0%, and 70.0% in sarcopenia versus 26.7%, 28.3%, and 27.5% without sarcopenia (all reported P<0.001). In alcohol-related cirrhosis, the CYP2C9 Arg144Cys Cys allele was 27.5% in sarcopenia versus 12.5% without sarcopenia and 1.2% in controls; the dissertation reported RR=22.0 and OR=29.97 for sarcopenia versus controls.

Conclusions: The dissertation data support an association between sarcopenia and enrichment of CYP2C9 Leu/Cys, SOD2 Val, and TGFβ1 Pro variants across major cirrhosis etiologies. These findings are hypothesis-generating and require external replication, adjustment for confounders, and reconciliation of subgroup denominators before journal submission.

Keywords:

liver cirrhosis, sarcopenia, CYP2C9, SOD2, TGFβ1, genetic polymorphism, oxidative stress, fibrosis

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