Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지
DOI QR코드

DOI QR Code

Putative Association of ITGB1 Haplotype with the Clearance of HBV Infection

  • Park, Tae-Joon (Department of Life Science, Sogang University) ;
  • Chun, Ji-Yong (Department of Life Science, Sogang University) ;
  • Bae, Joon-Seol (Department of Life Science, Sogang University) ;
  • Kim, Ja-Son Y. (Department of Life Science, Sogang University) ;
  • Lee, Jin-Sol (Department of Life Science, Sogang University) ;
  • Pasaje, Charisse Flerida (Department of Life Science, Sogang University) ;
  • Park, Byung-Lae (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Cheong, Hyun-Sub (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Lee, Hyo-Suk (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Kim, Yoon-Jun (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Shin, Hyoung-Doo (Department of Life Science, Sogang University)
  • Published : 2010.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (${\beta}1$) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and $P^{corr}=0.05$). The minor allele frequency (MAF) of ITGB1 haplotype -2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.

Keywords

References

  1. Barrett, J.C., Fry, B., Maller, J., and Daly, M.J. (2005). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263-265. https://doi.org/10.1093/bioinformatics/bth457
  2. Bridger, P.S., Haupt, S., Leiser, R., Johnson, G.A., Burghardt, R.C., Tinneberg, H.R., and Pfarrer, C. (2008). Integrin activation in bovine placentomes and in car-uncular epithelial cells isolated from pregnant cows. Biol. Reprod. 79, 274-282. https://doi.org/10.1095/biolreprod.108.067637
  3. Bruix, J., Sherman, M., Llovet, J.M., Beaugrand, M., Lencioni, R., Burroughs, A.K., Christensen, E., Pagliaro, L., Colombo, M., and Rodes, J. (2001). Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J. Hepatol. 35, 421-430. https://doi.org/10.1016/S0168-8278(01)00130-1
  4. Carlson, T.R., Hu, H., Braren, R., Kim, Y.H., and Wang, R.A. (2008). Cell-autonomous requirement for beta1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice. Development 135, 2193-2202. https://doi.org/10.1242/dev.016378
  5. Chang, J.J., Wightman, F., Bartholomeusz, A., Ayres, A., Kent, S.J., Sasadeusz, J., and Lewin, S.R. (2005). Reduced hepatitis B virus (HBV)-specific CD4+ T-cell responses in human immunodeficiency virus type 1-HBV-coinfected individuals receiving HBV-active antiretroviral therapy. J. Virol. 79, 3038-3051. https://doi.org/10.1128/JVI.79.5.3038-3051.2005
  6. Correia, C., Coutinho, A.M., Almeida, J., Lontro, R., Lobo, C., Miguel, T.S., Martins, M., Gallagher, L., Conroy, J., Gill, M., Oliveira, G., and Vicente, A.M. (2009). Association of the alpha4 integrin subunit gene (ITGA4) with autism. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 150B, 1147-1151. https://doi.org/10.1002/ajmg.b.30940
  7. Garrido, J.J., Jimenez-Marin, A.M., Yerle, M., de Andres-Cara, D.F., Morera, L., Llanes, D., and Barbancho, M.J. (2001). Assignment of the ITGB1 (integrin beta1 subunit) gene to pig chromosome band 10q17 with somatic cell hybrids. Cytogenet. Cell Genet. 94, 84-85. https://doi.org/10.1159/000048789
  8. Kim, Y.J., Lee, H.S., Im, J.P., Min, B.H., Kim, H.D., Jeong, J.B., Yoon, J.H., Kim, C.Y., Kim, M.S., Kim, J.Y., Jung, J.H., Kim, L.H., Park, B.L., and Shin, H.D. (2003a). Association of transforming growth factor-beta1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection. Exp. Mol. Med. 35, 196-202. https://doi.org/10.1038/emm.2003.27
  9. Kim, Y.J., Lee, H.S., Yoon, J.H., Kim, C.Y., Park, M.H., Kim, L.H., Park, B.L., and Shin, H.D. (2003b). Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection. Hum. Mol. Genet. 12, 2541-2546. https://doi.org/10.1093/hmg/ddg262
  10. Kim, Y.S., Cheong, J.Y., Cho, S.W., Lee, K.M., Hwang, J.C., Oh, B., Kimm, K., Lee, J.A., Park, B.L., Cheong, H.S., Shin, H.D., and Kim, J.H. (2009). A functional SNP of the interleukin-18 gene is associated with the presence of hepatocellular carcinoma in hepatitis B virus-infected patients. Dig. Dis. Sci. 54, 2722-2728. https://doi.org/10.1007/s10620-009-0970-6
  11. Lara-Pezzi, E., Majano, P.L., Yanez-Mo, M., Gomez-Gonzalo, M., Carretero, M., Moreno-Otero, R., Sanchez-Madrid, F., and Lopez-Cabrera, M. (2001). Effect of the hepatitis B virus HBx protein on integrin-mediated adhesion to and migration on extracellular matrix. J. Hepatol. 34, 409-415. https://doi.org/10.1016/S0168-8278(00)00090-8
  12. Lee, M.S., Kim, D.H., Kim, H., Lee, H.S., Kim, C.Y., Park, T.S., Yoo, K.Y., Park, B.J., and Ahn, Y.O. (1998). Hepatitis B vaccination and reduced risk of primary liver cancer among male adults: a cohort study in Korea. Int. J. Epidemiol. 27, 316-319. https://doi.org/10.1093/ije/27.2.316
  13. Lee, S.K., Kim, M.H., Cheong, J.Y., Cho, S.W., Yang, S.J., and Kwack, K. (2009). Integrin alpha V polymorphisms and haplotypes in a Korean population are associated with susceptibility to chronic hepatitis and hepatocellular carcinoma. Liver Int. 29, 187-195. https://doi.org/10.1111/j.1478-3231.2008.01843.x
  14. Lin, C.L., Liao, L.Y., Wang, C.S., Chen, P.J., Lai, M.Y., Chen, D.S., and Kao, J.H. (2005). Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B. Liver Int. 25, 564-570. https://doi.org/10.1111/j.1478-3231.2005.01041.x
  15. Livak, K.J. (1999). Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet. Anal. 14, 143-149. https://doi.org/10.1016/S1050-3862(98)00019-9
  16. Menashe, I., Rosenberg, P.S., and Chen, B.E. (2008). PGA: power calculator for case-control genetic association analyses. BMC Genet. 9, 36.
  17. Merican, I., Guan, R., Amarapuka, D., Alexander, M.J., Chutaputti, A., Chien, R.N., Hasnian, S.S., Leung, N., Lesmana, L., Phiet, P.H., Sjalfoellah Noer, H.M., Sollano, J., Sun, H.S., and Xu, D.Z. (2000). Chronic hepatitis B virus infection in Asian countries. J. Gastroenterol. Hepatol. 15, 1356-1361. https://doi.org/10.1046/j.1440-1746.2000.0150121356.x
  18. Mori, R., Ishiguro, H., Kuwabara, Y., Kimura, M., Mitsui, A., Tomoda, K., Mori, Y., Ogawa, R., Katada, T., Harata, K., and Fujii, Y. (2008). Targeting beta1 integrin restores sensitivity to docetaxel of esophageal squamous cell carcinoma. Oncol. Rep. 20, 1345-1351.
  19. Ng, C.C., Yew, P.Y., Puah, S.M., Krishnan, G., Yap, L.F., Teo, S.H., Lim, P.V., Govindaraju, S., Ratnavelu, K., Sam, C.K., Takahashi, A., Kubo, M., Kamatani, N., Nakamura, Y., and Mushiroda, T. (2009). A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma. J. Hum. Genet. 54, 392-397. https://doi.org/10.1038/jhg.2009.49
  20. Nyholt, D.R. (2004). A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am. J. Hum. Genet. 74, 765-769. https://doi.org/10.1086/383251
  21. O'Doherty, C., Roos, I.M., Antiguedad, A., Aransay, A.M., Hillert, J., and Vandenbroeck, K. (2007). ITGA4 polymorphisms and susceptibility to multiple sclerosis. J. Neuroimmunol. 189, 151-157. https://doi.org/10.1016/j.jneuroim.2007.07.006
  22. Park, B.L., Kim, Y.J., Cheong, H.S., Lee, S.O., Han, C.S., Yoon, J.H., Park, J.H., Chang, H.S., Park, C.S., Lee, H.S., and Shin, H.D. (2007). HDAC10 promoter polymorphism associated with development of HCC among chronic HBV patients. Biochem. Biophys Res. Commun. 363, 776-781. https://doi.org/10.1016/j.bbrc.2007.09.026
  23. Patil, M.A., Lee, S.A., Macias, E., Lam, E.T., Xu, C., Jones, K.D., Ho, C., Rodriguez-Puebla M., and Chen, X. (2009). Role of cyclin D1 as a mediator of c-Met- and beta-catenin-induced hepatocarcinogenesis. Cancer Res. 69, 253-261. https://doi.org/10.1158/0008-5472.CAN-08-2514
  24. Shin, H.D., Park, B.L., Cheong, H.S., Yoon, J.H., Kim, Y.J., and Lee, H.S. (2007). SPP1 polymorphisms associated with HBV clearance and HCC occurrence. Int. J. Epidemiol. 36, 1001-1008. https://doi.org/10.1093/ije/dym093
  25. Shin, H.D., Park, B.L., Kim, L.H., Jung, J.H., Kim, J.Y., Yoon, J.H., Kim, Y.J., and Lee, H.S. (2003). Interleukin 10 haplotype associated with increased risk of hepatocellular carcinoma. Hum. Mol. Genet. 12, 901-906. https://doi.org/10.1093/hmg/ddg104
  26. Stephens, M., Smith, N.J., and Donnelly, P. (2001). A new statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet. 68, 978-989. https://doi.org/10.1086/319501
  27. Streuli, C.H., and Akhtar, N. (2009). Signal co-operation between integrins and other receptor systems. Biochem. J. 418, 491-506. https://doi.org/10.1042/BJ20081948