title: HDAC10 promoter polymorphism associated with development of HCC among chronic HBV patients.
abstract: Histone deacetylases (HDACs) are key enzymes responsible for the removal of acetyl groups from acetylated histone and non-histone proteins, and play important roles in various biological processes including transcription regulation and DNA repair. In this study, we identified 22 sequence variants by direct DNA sequencing in 24 individuals and five common variant were selected for genotyping in larger-scale subjects (n=1095). Statistical analysis revealed that HDAC10-589C>T was significantly associated with HCC occurrence among chronic HBV patients (OR=2.39, P(cor)=0.04) as well as HCC acceleration among chronic HBV patients (RH=1.97, Pcor=0.002). Functional assay also revealed that luciferase activity of "T" allele was significantly higher than that of "C" allele of HDAC10-589C>T (P=0.023). These results suggest that the "T" allele of HDAC10-589C>T affect on the increased transcription activity, and might accelerate HCC development through increased expression of HDAC10.
authors: Department of Genetic Epidemiology, SNP Genetics, Inc, Room 1407, 14th floor, Complex B, WooLim Lion's Valley, 371-28, Gasan-Dong, Geumcheon-Gu, Seoul 153-803, Republic of Korea.
authors: Byung Lae
authors: BL
authors: Park
authors: Yoon Jun
authors: YJ
authors: Kim
authors: Hyun Sub
authors: HS
authors: Cheong
authors: Soo Ok
authors: SO
authors: Lee
authors: Chang Soo
authors: CS
authors: Han
authors: Jung-Hwan
authors: JH
authors: Yoon
authors: Ju Hyun
authors: JH
authors: Park
authors: Hun Soo
authors: HS
authors: Chang
authors: Choon-Sik
authors: CS
authors: Park
authors: Hyo-Suk
authors: HS
authors: Lee
authors: Hyoung Doo
authors: HD
authors: Shin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis / Q000706:statistics & numerical data; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016016:Proportional Hazards Models; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D011993:Recombinant Fusion Proteins; D008156:Luciferases; C447828:HDAC10 protein, human; D006655:Histone Deacetylases