BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

A replication study of genome-wide CNV association for hepatic biomarkers identifies nine genes associated with liver function

  • Kim, Hyo-Young (Department of Agricultural Biotechnology and the Research Institute for Agriculture and Life Science, Seoul National University) ;
  • Byun, Mi-Jeong (Department of Agricultural Biotechnology and the Research Institute for Agriculture and Life Science, Seoul National University) ;
  • Kim, Hee-Bal (Department of Agricultural Biotechnology and the Research Institute for Agriculture and Life Science, Seoul National University)
  • Received : 2011.05.17
  • Accepted : 2011.07.07
  • Published : 2011.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are biochemical markers used to test for liver diseases. Copy number variation (CNV) plays an important role in determining complex traits and is an emerging area in the study various diseases. We performed a genome-wide association study with liver function biomarkers AST and ALT in 407 unrelated Koreans. We assayed the genome-wide variations on an Affymetrix Genome-Wide 6.0 array, and CNVs were analyzed using HelixTree. Using single linear regression, 32 and 42 CNVs showed significance for AST and ALT, respectively (P value < 0.05). We compared CNV-based genes between the current study (KARE2; AST-140, ALT-172) and KARE1 (AST-1885, ALT-773) using NetBox. Results showed 9 genes (CIDEB, DFFA, PSMA3, PSMC5, PSMC6, PSMD12, PSMF1, SDC4, and SIAH1) were overlapped for AST, but no overlapped genes were found for ALT. Functional gene annotation analysis shown the proteasome pathway, Wnt signaling pathway, programmed cell death, and protein binding.

Keywords

References

  1. Yap, C. and Aw, T. (2010) Liver Function Tests (LFTs). Proceedings of Singapore Healthcare 19, 80-82. https://doi.org/10.1177/201010581001900113
  2. Sheth, S., Flamm, S., Gordon, F. and Chopra, S. (1998) AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am. J. Gastroenterol. 93, 44-48. https://doi.org/10.1111/j.1572-0241.1998.044_c.x
  3. Cohen, J. and Kaplan, M. (1979) The SGOT/SGPT ratio--an indicator of alcoholic liver disease. Dig. Dis. Sci. 24, 835-838. https://doi.org/10.1007/BF01324898
  4. Clemenz, M., Frost, N., Schupp, M., Caron, S., Foryst-Ludwig, A., Bohm, C., Hartge, M., Gust, R., Staels, B. and Unger, T. (2008) Liver-Specific Peroxisome Proliferator- Activated Receptor Ya Target Gene Regulation by the Angiotensin Type 1 Receptor Blocker Telmisartan. Diabetes 57, 1405-1413. https://doi.org/10.2337/db07-0839
  5. Feuk, L., Carson, A. and Scherer, S. (2006) Structural variation in the human genome. Nat. Rev. Genet. 7, 85-97.
  6. Estivill, X. and Armengol, L. (2007) Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies. PLoS Genet 3, 1787-1799.
  7. Perry, G., Ben-Dor, A., Tsalenko, A., Sampas, N., Rodriguez-Revenga, L., Tran, C., Scheffer, A., Steinfeld, I., Tsang, P. and Yamada, N. (2008) The fine-scale and complex architecture of human copy-number variation. Am. J. Hum. Genet. 82, 685-695. https://doi.org/10.1016/j.ajhg.2007.12.010
  8. de Stahl, T., Sandgren, J., Piotrowski, A., Nord, H., Andersson, R., Menzel, U., Bogdan, A., Thuresson, A., Poplawski, A. and von Tell, D. (2008) Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC clone based array. Hum. Mutat. 29, 398-408. https://doi.org/10.1002/humu.20659
  9. Redon, R., Ishikawa, S., Fitch, K., Feuk, L., Perry, G., Andrews, T., Fiegler, H., Shapero, M., Carson, A. and Chen, W. (2006) Global variation in copy number in the human genome. Nature 444, 444-454. https://doi.org/10.1038/nature05329
  10. Stranger, B., Forrest, M., Dunning, M., Ingle, C., Beazley, C., Thorne, N., Redon, R., Bird, C., de Grassi, A. and Lee, C. (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315, 848-853. https://doi.org/10.1126/science.1136678
  11. Beckmann, J., Estivill, X. and Antonarakis, S. (2007) Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability. Nat. Rev. Genet. 8, 639-646.
  12. Hastings, P., Lupski, J., Rosenberg, S. and Ira, G. (2009) Mechanisms of change in gene copy number. Nat. Rev. Genet. 10, 551-564.
  13. Kim, H., Cho, S., Yu, J., Sung, S. and Kim, H. (2010) Analysis of copy number variation in 8,842 Korean individuals reveals 39 genes associated with hepatic biomarkers AST and ALT. BMB Rep. 43, 547-553. https://doi.org/10.5483/BMBRep.2010.43.8.547
  14. Yim, S., Kim, T., Hu, H., Kim, J., Kim, B., Lee, J., Han, B., Shin, S., Jung, S. and Chung, Y. (2009) Copy number variations in East-Asian population and their evolutionary and functional implications. Hum. Mol. Genet. 19, 1001-1008.
  15. Donohue, Jr, T., Cederbaum, A., French, S., Barve, S., Gao, B. and Osna, N. (2007) Role of the Proteasome in Ethanol Induced Liver Pathology. Alcohol. Clin. Exp. Res. 31, 1446-1459. https://doi.org/10.1111/j.1530-0277.2007.00454.x
  16. Donohue, Jr, T. (2002) The ubiquitin proteasome system and its role in ethanol induced disorders. Addict. Biol. 7, 15-28. https://doi.org/10.1080/135562101200100562
  17. Armengol, C., Cairo, S., Fabre, M. and Buendia, M. (2009) Wnt signaling and hepatocarcinogenesis: The hepatoblastoma model. Int. J. Biochem. Cell Biol. 43, 265-270.
  18. Okabe, H., Satoh, S., Furukawa, Y., Kato, T., Hasegawa, S., Nakajima, Y., Yamaoka, Y. and Nakamura, Y. (2003) Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer Res. 63, 3043-3048.
  19. Saad, A., Aziz, A., Yehia, I., El-Ghareeb, A. and Ismail, H. (2009) Programmed Cell Death in the Liver of Different Species of Anuran Amphibians During Metamorphosis. Australian Journal of Basic and Applied Sciences 3, 4644-4655.
  20. Inohara, N., Koseki, T., Chen, S., Wu, X. and Nunez, G. (1998) CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor. EMBO J. 17, 2526-2533. https://doi.org/10.1093/emboj/17.9.2526
  21. Li, J., Ye, J., Xue, B., Qi, J., Zhang, J., Zhou, Z., Li, Q., Wen, Z. and Li, P. (2007) Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation. Diabetes 56, 2523. https://doi.org/10.2337/db07-0040
  22. Ye, J., Li, J., Liu, Y., Li, X., Yang, T., Ma, X., Li, Q., Yao, Z. and Li, P. (2009) Cideb, an ER-and Lipid Droplet- Associated Protein, aMediates VLDL Lipidation and Maturation byaInteracting with Apolipoprotein B. Cell Metab. 9, 177-190. https://doi.org/10.1016/j.cmet.2008.12.013
  23. Li, Z. (2007) To study the physiological role of cideb protein by using cideb knockout mice as a model system.
  24. Blaschke, T. (1977) Protein binding and kinetics of drugs in liver diseases. Clin. Pharmacokinet. 2, 32-44. https://doi.org/10.2165/00003088-197702010-00003
  25. Jahnchen, E., Blanck, K., Breuing, K., Gilfrich, H., Meinertz, T. and Trenk, D. (1981) Plasma protein binding of azapropazone in patients with kidney and liver disease. Br. J. Clin. Pharmacol. 11, 361-367. https://doi.org/10.1111/j.1365-2125.1981.tb01133.x
  26. Kojima, T., Shworak, N. and Rosenberg, R. (1992) Molecular cloning and expression of two distinct cDNA-encoding heparan sulfate proteoglycan core proteins from a rat endothelial cell line. J. Biol. Chem. 267, 4870-4877.
  27. Rioux, V., Landry, R. and Bensadoun, A. (2002) Sandwich immunoassay for the measurement of murine syndecan-4. J. Lipid Res. 43, 167-173.
  28. Cerami, E., Demir, E., Schultz, N., Taylor, B. and Sander, C. (2010) Automated network analysis identifies core pathways in glioblastoma. PLoS One 5, 1-10.
  29. Ding, L., Wendl, M., Koboldt, D. and Mardis, E. (2010) Analysis of Next Generation Genomic Data in Cancer: Accomplishments and Challenges. Hum. Mol. Genet. 1, R188-R196.
  30. Bax, L., Yu, L., Ikeda, N., Tsuruta, H. and Moons, K. (2006) Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Med. Res. Methodol. 6, 50. https://doi.org/10.1186/1471-2288-6-50
  31. Richert, L., Liguori, M., Abadie, C., Heyd, B., Mantion, G., Halkic, N. and Waring, J. (2006) Gene expression in human hepatocytes in suspension after isolation is similar to the liver of origin, is not affected by hepatocyte cold storage and cryopreservation, but is strongly changed after hepatocyte plating. Drug Metab. Dispos. 34, 870-879. https://doi.org/10.1124/dmd.105.007708
  32. Lambert, C. (2005) HelixTree¢ç Genetics Analysis Software. Golden Helix. Inc. http//www.goldenhelix.com.
  33. Shannon, P., Markiel, A., Ozier, O., Baliga, N., Wang, J., Ramage, D., Amin, N., Schwikowski, B. and Ideker, T. (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498-2504. https://doi.org/10.1101/gr.1239303
  34. Dennis Jr, G., Sherman, B., Hosack, D., Yang, J., Gao, W., Lane, H. and Lempicki, R. (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4, P3. https://doi.org/10.1186/gb-2003-4-5-p3
  35. Harris, M., Clark, J., Ireland, A., Lomax, J., Ashburner, M., Foulger, R., Eilbeck, K., Lewis, S., Marshall, B. and Mungall, C. (2004) The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 32, D258-D261. https://doi.org/10.1093/nar/gkh036
  36. Kanehisa, M., Goto, S., Kawashima, S. and Nakaya, A. (2002) The KEGG databases at GenomeNet. Nucleic Acids Res. 30, 42-46. https://doi.org/10.1093/nar/30.1.42

Cited by

  1. Semantic networks for genome-wide CNV associated with AST and ALT in Korean cohorts vol.9, pp.2, 2013, https://doi.org/10.1007/s13273-013-0014-3
  2. Genome-Wide Scan for Copy Number Variation Association with Biomarker Quantitative Trait Loci in Aging vol.12, pp.2, 2014, https://doi.org/10.1177/1721727X1401200206
  3. VCS: Tool for Visualizing Copy Number Variation and Single Nucleotide Polymorphism vol.27, pp.12, 2014, https://doi.org/10.5713/ajas.2014.14143