Genetic association of complement component 2 variants with chronic hepatitis B in a Korean population

Liver Int. 2018 Sep;38(9):1576-1582. doi: 10.1111/liv.13675. Epub 2018 Feb 10.

Abstract

Background & aims: Numerous single nucleotide polymorphisms associated with an increased risk of liver diseases, chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma have been identified. In this study, we scrutinized the genetic effects of C2 variants, which were conflicting in previous results, on the risk of chronic hepatitis B in a Korean population.

Methods: We genotyped 22 common C2 genetic variants of 977 chronic hepatitis B cases including 302 chronic hepatitis B-related hepatocellular carcinoma cases and 785 population controls. Statistical analysis was performed to examine the effects of genotype on the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma.

Results: Logistic regression analyses showed that six C2 single nucleotide polymorphisms had significant associations with the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma among the Korean subjects. Stepwise analysis revealed that causal markers (rs9267665 and rs10947223) were identified among the C2 variants (stepwise P = 3.32 × 10-9 and 2.04 × 10-5 respectively). In further conditional analysis with previous chronic hepatitis B-associated loci, these two single nucleotide polymorphisms were independently associated with the risk of chronic hepatitis B. In addition, we investigated the ability of genetic risk scores combining 12 multi-chronic hepatitis B loci to predict the risk of chronic hepatitis B. Individuals with higher genetic risk scores showed increased risk for chronic hepatitis B.

Conclusions: Our results suggested that the C2 gene might be a susceptibility locus for chronic hepatitis B in Korean populations. The cumulative genetic effects may contribute to future etiological explanations for chronic hepatitis B.

Keywords: chronic hepatitis B; complement component 2; genetic risk score; single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Case-Control Studies
  • Complement C2 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Republic of Korea
  • Risk Factors

Substances

  • Complement C2