title: YKL-40 genetic polymorphisms and the risk of liver disease progression in patients with advanced fibrosis due to chronic hepatitis C.
abstract: OBJECTIVE
  The aim of this study was to explore the association of a functional YKL-40 promoter polymorphism (rs4950928) with baseline disease stage, response to antiviral therapy and risk of liver disease progression in a group of patients with chronic hepatitis C (CHC).
  
  
  METHODS
  YKL-40 promoter polymorphisms were determined in 456 Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial patients with bridging fibrosis or cirrhosis entering a prerandomization lead-in peginterferon/ribavirin 24-week treatment phase and in 462 patients followed for a mean of 3.8 years after randomization to maintenance peginterferon or observation.
  
  
  RESULTS
  Mean patient age was 49.5 years, 70.4% were men and 71.2% were Caucasian. The 17% frequency of the YKL-40 minor allele (T) was similar to that reported in the general population. YKL-40 genotype was associated significantly with baseline serum YKL-40 levels but was not associated with the likelihood of a virological response following 24-48 weeks of peginterferon/ribavirin therapy. Serum YKL-40 levels remained significantly lower during follow-up in the randomized TT homozygotes compared with CT heterozygotes and CC homozygotes (P < 0.001). Despite this association, YKL-40 genotype was not associated with the risk of clinical or histological liver disease progression.
  
  
  CONCLUSIONS
  A reduced frequency of the protective YKL-40 promoter polymorphism was not observed in the HALT-C Trial patient population. The absence of an association between YKL-40 promoter polymorphisms and baseline liver disease severity as well as with the risk of liver disease progression over time suggests that this polymorphism is not associated with disease progression in CHC patients with established fibrosis.
authors: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0362, USA. rfontana@med.umich.edu
authors: Robert J
authors: RJ
authors: Fontana
authors: Heather J
authors: HJ
authors: Litman
authors: Jules L
authors: JL
authors: Dienstag
authors: Herbert L
authors: HL
authors: Bonkovsky
authors: Grace
authors: G
authors: Su
authors: Richard K
authors: RK
authors: Sterling
authors: Anna S
authors: AS
authors: Lok
mesh_terms: D054392:Adipokines / Q000097:blood / Q000235:genetics*; D000328:Adult; D000071451:Chitinase-3-Like Protein 1; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D037102:Lectins / Q000097:blood / Q000235:genetics*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D016898:Interferon-alpha; D037102:Lectins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a