title: VKORC1 haplotypes influence the performance characteristics of PIVKAII for screening of hepatocellular carcinoma.
abstract: BACKGROUND
  PIVKAII (protein induced by vitamin K absence), used for screening for hepatocellular carcinoma (HCC), is influenced by vitamin K epoxide reductase complex subunit 1 (VKORC1). VKORC1 haplotype frequency is significantly different in ethnic groups. We evaluated whether VKORC1 haplotypes could influence the performance characteristics of PIVKAII in screening for HCC.
  
  
  METHODS
  A total 228 HCC patients and 258 patients with hepatitis B were recruited. Tumor size was measured in 76 patients with HCC. Serum PIVKAII concentrations and VKORC1 haplotype were determined in the cohort. Youden's index and ROC curves were used to compare the performance characteristics of PIVKAII in screening for HCC.
  
  
  RESULTS
  In the HCC group and in patients with hepatitis B, serum PIVKAII concentrations were higher in VKORC1 rs2395612 TT carriers than in CC/CT carriers (50.34±72.18 vs. 11.98±27.45, p<0.05 in HCC group and 1.92±0.52 vs. 1.48±0.36, p<0.01). The estimated optimal cut-off value of PIVKAII for screening HCC was 2.0 and 3.0 ng/mL in CC/CT carriers and TT carriers, respectively. Furthermore, VKORC1 haplotypes also influenced the association of serum PIVKAII concentrations with HCC tumor size in patients with HCC.
  
  
  CONCLUSIONS
  VKORC1 haplotypes influence the performance characteristics of PIVKAII for screening of HCC. Thus, measurement could be complementary for PIVKAII in HCC screening.
authors.affiliation: Sino-German Laboratory for Molecular Medicine, FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China. yibowang@hotmail.com
authors.forename: Yibo
authors.initials: Y
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Luo
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Fan
authors.forename: Jinxing
authors.initials: J
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rutai
authors.initials: R
authors.lastname: Hui
mesh_terms: D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D006239:Haplotypes; D006509:Hepatitis B / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011498:Protein Precursors / Q000097:blood / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; C008208:acarboxyprothrombin; D011516:Prothrombin; D004247:DNA; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases