Advertisement

Effects of variant rs346473 in ARHGAP24 gene on disease progression of HBV infection in han Chinese population

  • Lifeng Liu (刘丽凤)
  • Jinjian Yao (姚津剑)
  • Jin Li (里 进)
  • Jinliang Zhang (张金良)
  • Jinling Yu (余金玲)
  • Xiaorui Jiang (姜小瑞)
  • Shuzhen Sun (孙淑珍)
  • Qing Liu (刘 庆)
  • Ying Chang (常 莹)
  • Yongwen He (贺永文)
  • Jusheng Lin (林菊生)
Article

Summary

Host genetic, environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus (HBV) infection. The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24 (ARHGAP24) gene and disease progression of HBV infection in Han Chinese population. These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers, and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers (AsC) in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase. Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase (OR, 2.693; 95% CI, 1.928–3.760; P=6.2×10−9; additive model) and the replication phase (OR, 1.490; 95% CI, 1.104–2.012; P=9.0×10−3; additive model). These two SNPs were in strong linkage disequilibrium with D′=0.99 and r 2=0.951, and haplotype TT disclosed an increased susceptibility to HBV progression (OR, 1.980; 95% CI, 1.538–2.545; P=8.1×10−8). These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.

Key words

ARHGAP24 gene single nucleotide polymorphisms HBV progression 

References

  1. 1.
    Frodsham AJ. Host genetics and the outcome of hepatitis B viral infection. Transpl Immunol, 2005,14(3–4):183–186PubMedCrossRefGoogle Scholar
  2. 2.
    Prevention UCfDCa. CDC Travel’s Health-2010 Yellow Book, Chapter 2 - Hepatitis B. (updated 6 October 2009, Accessed 18 June 2010) available from http:/wwwnc.cdc.gov/travel/yellowbook/2010/Chapter 2/Hepatitis b.as px.
  3. 3.
    Thursz M. Genetic susceptibility in chronic viral hepatitis. Antiviral Res, 2001,52(2):113–116PubMedCrossRefGoogle Scholar
  4. 4.
    Chu CJ, Lok AS. Clinical significance of hepatitis B virus genotypes. Hepatology, 2002,35(5):1274–1276PubMedCrossRefGoogle Scholar
  5. 5.
    Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer, 1988,61(10):1942–1956PubMedCrossRefGoogle Scholar
  6. 6.
    Geier A, Gartung C, Dietrich CG. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med, 2002,347(21):1721–1722PubMedCrossRefGoogle Scholar
  7. 7.
    Chen CJ, Yang HI, Iloeje UH. Hepatitis B virus DNA levels and outcomes in chronic hepatitis B. Hepatology, 2009,49(5 Suppl):S72–84PubMedCrossRefGoogle Scholar
  8. 8.
    Hu X, Lin J, Xie Q, et al. DNA double-strand breaks, potential targets for HBV integration. J Huazhong Univ Sci Technolog Med Sci, 2010,30(3):265–270PubMedCrossRefGoogle Scholar
  9. 9.
    Wang J, Lin J, Chang Y, et al. MCM3AP, a novel HBV integration site in hepatocellular carcinoma and its implication in hepatocarcinogenesis. J Huazhong Univ Sci Technolog Med Sci, 2010,30(4):425–429PubMedCrossRefGoogle Scholar
  10. 10.
    Lin TM, Chen CJ, Wu MM, et al. Hepatitis B virus markers in Chinese twins. Anticancer Res, 1989,9(3):737–741PubMedGoogle Scholar
  11. 11.
    Demir G, Belentepe S, Ozguroglu M, et al. Simultaneous presentation of hepatocellular carcinoma in identical twin brothers. Med Oncol, 2002,19(2):113–116PubMedCrossRefGoogle Scholar
  12. 12.
    He YL, Zhao YR, Zhang SL, et al. Host susceptibility to persistent hepatitis B virus infection. World J Gastroenterol, 2006,12(30):4788–4793PubMedGoogle Scholar
  13. 13.
    Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature, 1996,382(6593):722–725PubMedCrossRefGoogle Scholar
  14. 14.
    Jin Q, Agrawal L, Meyer L, et al. CCR5Delta32 59537-G/A promoter polymorphism is associated with low translational efficiency and the loss of CCR5Delta32 protective effects. J Virol 2008,82(5):2418–2426PubMedCrossRefGoogle Scholar
  15. 15.
    Kamatani Y, Wattanapokayakit S, Ochi H, et al. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat Genet, 2009,41(5):591–595PubMedCrossRefGoogle Scholar
  16. 16.
    Zhang H, Zhai Y, Hu Z, et al. Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers. Nat Genet, 2010,42(9):755–758Google Scholar
  17. 17.
    Parasitology C. The sixth Chinese national conference on virus hepatitis: prevention and treatment of virus hepatitis (draft). Chin J Internal Med, 2000,44:788–789Google Scholar
  18. 18.
    Ganem D, Prince AM. Hepatitis B virus infection-natural history and clinical consequences. N Engl J Med, 2004, 350(11):1118–1129PubMedCrossRefGoogle Scholar
  19. 19.
    Meaburn E, Butcher LM, Schalkwyk LC, et al. Genotyping pooled DNA using 100K SNP microarrays: a step towards genomewide association scans. Nucleic Acids Res, 2006,34(4):e27PubMedCrossRefGoogle Scholar
  20. 20.
    Pearson JV, Huentelman MJ, Halperin RF, et al. Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies. Am J Hum Genet, 2007, 80(1):126–139PubMedCrossRefGoogle Scholar
  21. 21.
    Lovmar L, Ahlford A, Jonsson M, et al. Silhouette scores for assessment of SNP genotype clusters. BMC Genomics, 2005,6:35PubMedCrossRefGoogle Scholar
  22. 22.
    Sham P, Bader JS, Craig I, et al. DNA Pooling: a tool for large-scale association studies. Nat Rev Genet, 2002,3(11) 862–871PubMedCrossRefGoogle Scholar
  23. 23.
    Baum AE, Akula N, Cabanero M, et al. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry, 2008,13(2):197–207PubMedCrossRefGoogle Scholar
  24. 24.
    Shifman S, Johannesson M, Bronstein M, et al. Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genet, 2008,4(2):e28PubMedCrossRefGoogle Scholar
  25. 25.
    Bosse Y, Bacot F, Montpetit A, et al. Identification of susceptibility genes for complex diseases using pooling-based genome-wide association scans. Hum Genet, 2009,125(3):305–318PubMedCrossRefGoogle Scholar
  26. 26.
    Huo T, Wu JC, Hwang SJ, et al. Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in a longitudinal study. Eur J Gastroenterol Hepatol, 2000,12(6):687–693PubMedCrossRefGoogle Scholar
  27. 27.
    Chan HL, Tse CH, Mo F, et al. High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol, 2008, 26(2):177–182PubMedCrossRefGoogle Scholar
  28. 28.
    Park BK, Park YN, Ahn SH, et al. Long-term outcome of chronic hepatitis B based on histological grade and stage. J Gastroenterol Hepatol, 2007,22(3):383–388PubMedCrossRefGoogle Scholar
  29. 29.
    Moon SY, Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol, 2003,13(1):13–22PubMedCrossRefGoogle Scholar
  30. 30.
    Ohta Y, Hartwig JH, Stossel TP. FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling. Nat Cell Biol, 2006,8(8):803–814PubMedCrossRefGoogle Scholar
  31. 31.
    Su ZJ, Hahn CN, Goodall GJ, et al. A vascular cell-restricted RhoGAP, p73RhoGAP, is a key regulator of angiogenesis. Proc Natl Acad Sci USA, 2004,101(33): 12 212–12 217CrossRefGoogle Scholar
  32. 32.
    Ying J, Li H, Cui Y, et al. Epigenetic disruption of two proapoptotic genes MAPK10/JNK3 and PTPN13/FAP-1 in multiple lymphomas and carcinomas through hypermethylation of a common bidirectional promoter. Leukemia, 2006,20(6):1173–1175PubMedCrossRefGoogle Scholar
  33. 33.
    Tournier C, Hess P, Yang DD, et al. Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science, 2000,288(5467):870–874PubMedCrossRefGoogle Scholar
  34. 34.
    Holm H, Gudbjartsson DF, Arnar DO, et al. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet, 2010,42(2):117–122PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Lifeng Liu (刘丽凤)
    • 1
    • 2
  • Jinjian Yao (姚津剑)
    • 1
  • Jin Li (里 进)
    • 1
  • Jinliang Zhang (张金良)
    • 2
  • Jinling Yu (余金玲)
    • 1
  • Xiaorui Jiang (姜小瑞)
    • 1
  • Shuzhen Sun (孙淑珍)
    • 1
  • Qing Liu (刘 庆)
    • 1
  • Ying Chang (常 莹)
    • 1
  • Yongwen He (贺永文)
    • 3
  • Jusheng Lin (林菊生)
    • 1
  1. 1.Institute of Liver Disease, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Liaocheng People’s HospitalLiaochengChina
  3. 3.Department of Infection Disease, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations