Genetic variants associated with serum alanine aminotransferase levels among patients with hepatitis C virus infection: A genome-wide association study

Po Chun Liu, Chi Chan, Yu Han Huang, Yen Ju Chen, Shu Fen Liao, Yu Ju Lin, Claire Huang, Sheng Nan Lu, Chin Lan Jen, Li Yu Wang, Hwai I. Yang, Chen Yang Shen, Chien Jen Chen, Mei Hsuan Lee

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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 <10−5 were further tested for associations with serial ALT levels then validated in 486 anti-HCV seropositives. Multinomial logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals of SNPs associated with ALT. The SNP was evaluated for HCC risk by using Cox's proportional hazards models. After quality control, 803 participants with 564,464 SNPs were included in the analysis. Of these, 12 SNPs were associated with ALT (p < 10−5). Among the participants, 158 (19.7%) had ALT persistently ≤15 U/L, 327 (40.7%) ever >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 <.05). The A allele (vs C) of rs568800 was associated with ALT >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.

Original languageEnglish
Pages (from-to)1265-1273
Number of pages9
JournalJournal of Viral Hepatitis
Volume28
Issue number9
DOIs
Publication statusPublished - Sept 2021
Externally publishedYes

Keywords

  • ALT serial test
  • hepatocellular carcinoma
  • quantitative trait
  • Taiwan biobank

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

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