Information on genetic variants associated with elevated serum alanine aminotransferase (ALT) levels remains limited. A genome-wide association study was performed to identify single-nucleotide polymorphisms (SNPs) associated with ALT levels. The ALT-associated SNP was further evaluated for hepatocellular carcinoma (HCC) risk. A cohort of 892 anti-HCV seropositive patients was used for genome-wide SNP array to examine the associations with baseline ALT levels. SNPs 15 U/L but never >45 U/L, and 318 (39.6%) ever >45 U/L during follow-up. The rs568800 was associated with serial ALT levels, and this was replicated in the external population significantly (p 15 U/L but ≤45 U/L and ALT >45 U/L, with the adjusted ORs of 1.41 (1.11–1.78) and 1.86 (1.34–2.60), respectively. The adjusted HRs for HCC were 2.09 (0.90–4.89) for AC and 2.64 (1.13–6.17) for AA (CC as a reference). In conclusion, the rs568800 was associated with serum ALT levels and HCC risk. Clinical utility should be evaluated among patients who have received antivirals.
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