PMID- 23615070
OWN - NLM
STAT- MEDLINE
DCOM- 20140219
LR  - 20231213
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 14
IP  - 5
DP  - 2013 Jul-Aug
TI  - Polymorphisms in histone deacetylases improve the predictive value of IL-28B for 
      chronic hepatitis C therapy.
PG  - 317-24
LID - 10.1038/gene.2013.24 [doi]
AB  - Histone deacetylases (HDACs) influence many cellular processes, including the 
      modulation of signal transducer and activator of transcription activity (STAT) in 
      response to interferon (IFN). To identify genetic markers that help optimize the 
      IL-28B prediction of chronic hepatitis C (CHC) sustained virological response 
      (SVR), we evaluated 27 single-nucleotide polymorphisms (SNPs) in HDAC1-11. Three 
      SNPs, rs3778216, rs976552 and rs368328 in HDAC2, HDAC3 and HDAC5, respectively, 
      were independently associated with SVR (P<0.05). The addition of these three 
      HDAC's SNPs to the IL-28B predictive model (area under the curve (AUC)=0.630) 
      rendered an important improvement of AUC-receiver operating characteristic value 
      (AUC=0.747, P=0.021). Chi-squared Automatic Interaction Detector (CHAID) analysis 
      denoted the significance of the rs3778216 C/C genotype in identifying a group of 
      good responders despite carrying IL-28B T allele (79.2% of SVR), whereas HDAC5 G 
      allele characterized a subgroup with poor response rate (25.5%). However, HDAC3 
      rs976552 did not display a relevant role for the hierarchical classification of 
      patients. Variables related to SVR in hepatitis C virus genotype 1 (HCV-1) cohort 
      were the same of those obtained for the overall population. Interestingly, in 
      non-HCV-1 patients (n=56) the HDAC2 C/C genotype was the unique predictive 
      variable related to SVR (AUC=0.733, P<0.007). Thus, these preliminary results 
      suggest the potential usefulness of combined IL-28B and HDAC genotyping for the 
      CHC patients' classification by likelihood of an SVR.
FAU - Lopez-Rodriguez, R
AU  - Lopez-Rodriguez R
AD  - Liver Unit, Gastroenterology Service, Hospital Universitario de La Princesa, 
      Instituto de Investigacion Sanitaria Princesa (IIS-IP), Universidad Autonoma de 
      Madrid and CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
FAU - Hernandez-Bartolome, A
AU  - Hernandez-Bartolome A
FAU - Borque, M J
AU  - Borque MJ
FAU - Rodriguez-Munoz, Y
AU  - Rodriguez-Munoz Y
FAU - Martin-Vilchez, S
AU  - Martin-Vilchez S
FAU - Trapero-Marugan, M
AU  - Trapero-Marugan M
FAU - Garcia-Buey, L
AU  - Garcia-Buey L
FAU - Munoz de Rueda, P
AU  - Munoz de Rueda P
FAU - Rodrigo, L
AU  - Rodrigo L
FAU - Vidal-Castineira, J R
AU  - Vidal-Castineira JR
FAU - Salmeron, J
AU  - Salmeron J
FAU - Moreno-Otero, R
AU  - Moreno-Otero R
FAU - Sanz-Cameno, P
AU  - Sanz-Cameno P
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130425
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Antiviral Agents)
RN  - 0 (interferon-lambda, human)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukins)
RN  - 0 (Isoenzymes)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 49717AWG6K (Ribavirin)
RN  - 9008-11-1 (Interferons)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/therapeutic use
MH  - Drug Therapy, Combination
MH  - Female
MH  - Gene Frequency
MH  - Genotype
MH  - Hepacivirus/drug effects/genetics
MH  - Hepatitis C, Chronic/*drug therapy/genetics/virology
MH  - Histone Deacetylases/*genetics
MH  - Humans
MH  - Interferon-alpha/chemistry/therapeutic use
MH  - Interferons
MH  - Interleukins/*genetics
MH  - Isoenzymes/genetics
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Polyethylene Glycols/chemistry
MH  - *Polymorphism, Single Nucleotide
MH  - Prognosis
MH  - Ribavirin/therapeutic use
MH  - Treatment Outcome
MH  - Viral Load/drug effects/genetics
MH  - Young Adult
EDAT- 2013/04/26 06:00
MHDA- 2014/02/20 06:00
CRDT- 2013/04/26 06:00
PHST- 2013/01/05 00:00 [received]
PHST- 2013/03/07 00:00 [revised]
PHST- 2013/03/12 00:00 [accepted]
PHST- 2013/04/26 06:00 [entrez]
PHST- 2013/04/26 06:00 [pubmed]
PHST- 2014/02/20 06:00 [medline]
AID - gene201324 [pii]
AID - 10.1038/gene.2013.24 [doi]
PST - ppublish
SO  - Genes Immun. 2013 Jul-Aug;14(5):317-24. doi: 10.1038/gene.2013.24. Epub 2013 Apr 
      25.