This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. NRF-2015R1A2A1A15053987 and 2017R1D1A1B03030763), and grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI16C1074) and Samjin Pharm (Grant No. 800-20170260).

Handling Editor: Alexander Thompson

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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.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

Supporting Information

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Citing Literature

Volume38, Issue9

September 2018

Pages 1576-1582

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

Abstract

Background & Aims

Methods

Results

Conclusions

CONFLICT OF INTEREST

Supporting Information

REFERENCES

Citing Literature

References

Information

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

Abstract

Background & Aims

Methods

Results

Conclusions

CONFLICT OF INTEREST

Supporting Information

REFERENCES

Citing Literature

References

Related

Information