SINGLE NUCLEOTIDE POLYMORPHISMS IN TGF-Β1 AND THEIR ASSOCIATION WITH HCC DEVELOPMENT IN HCV PATIENTS

Background: Hepatitis C virus (HCV) infection remains a global public health concern, affecting over 170 million individuals and contributing substantially to the burden of liver-related morbidity and mortality. Chronic HCV infection can progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Cytokine gene polymorphisms, including transforming growth factor-beta 1 (TGF-β1), may influence individual susceptibility to HCC. Variations in the TGF-β1 promoter region, such as the −509 C/T polymorphism, can alter cytokine expression and potentially affect disease progression. Objective: To investigate the association between TGF-β1 −509 C/T gene polymorphism and the risk of developing HCC in patients with chronic HCV infection in a local Pakistani population. Methods: A comparative study was conducted involving 80 patients recruited from Sheikh Zayed Hospital, Lahore. Group I comprised 40 patients with chronic HCV infection without HCC, and Group II included 40 chronic HCV patients with HCC. Diagnosis of HCC was confirmed by abdominal ultrasound and computed tomography. Genotyping of TGF-β1 −509 C/T polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis. Statistical analysis was conducted using SPSS version 20.0, with chi-square tests to assess genotype and allele distribution. Odds ratios (OR) with 95% confidence intervals (CI) were calculated, and p < 0.05 was considered significant. Results: The TT genotype was present in 11 (39.3%) HCV patients and 17 (60.7%) HCC patients [OR = 2.511, 95% CI: 0.786–8.029, p = 0.120], while the CT genotype was detected in 16 (53.3%) HCV patients and 14 (46.7%) HCC patients [OR = 1.422, 95% CI: 0.457–4.427, p = 0.544]. No statistically significant association was observed between genotype distribution and HCC; however, individuals carrying the TT genotype or T allele exhibited a higher OR compared to those with the CC genotype. Conclusion: Although no significant association was found, the TGF-β1 −509 T allele may contribute to increased susceptibility to HCC in chronic HCV patients in the local population, highlighting the need for larger-scale studies.