HDAC10 promoter polymorphism associated with development of HCC among chronic HBV patients.
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.
Park
Byung Lae
BL
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.
Kim
Yoon Jun
YJ
Cheong
Hyun Sub
HS
Lee
Soo Ok
SO
Han
Chang Soo
CS
Yoon
Jung-Hwan
JH
Park
Ju Hyun
JH
Chang
Hun Soo
HS
Park
Choon-Sik
CS
Lee
Hyo-Suk
HS
Shin
Hyoung Doo
HD
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
D011993:Recombinant Fusion Proteins; D008156:Luciferases; C447828:HDAC10 protein, human; D006655:Histone Deacetylases