title: SNPs in the promoter region of the osteopontin gene as a possible host factor for sex difference in hepatocellular carcinoma development in patients with HCV.
abstract: OBJECTIVE
  Four single nucleotide polymorphisms (SNPs) exist in the promoter region of the osteopontin (OPN) gene, namely, the SNPs at nucleotide (nt) -155, -616, and -1748 showing linkage disequilibrium to each other, and an independent SNP at nt -443. The significance of these SNPs in the risk of hepatocellular carcinoma (HCC) development was examined in patients with hepatitis C virus (HCV).
  
  
  METHODS
  The SNPs at nt -155 and nt -443 were analyzed in 120 patients with HCC. The promoter activity was measured in HepG2 cells by the dual-luciferase reporter assay. The electrophoretic mobility shift assay was performed using nuclear extracts from the cells.
  
  
  RESULTS
  Peripheral platelet counts at the time of HCC detection were greater in women with homozygous deletion at nt -155 and C/C or C/T at nt -443 than in those showing other allelic combinations, while no such difference was observed in men. The promoter activity was greater in oligonucleotides with deletions at nt -155 and C at nt -443 than in those with other haplotypes. The mobility shift assay showed double and single complexes with oligonucleotides around nt -155 and nt -443, respectively. Binding activities were greater in deletion than in G in the case of the retarded complex in the former assay and in T than in C in the latter assay. The other complex in the former assay included SRY, showing an equivalent binding activity to oligonucleotides with both alleles.
  
  
  CONCLUSIONS
  OPN promoter SNPs may play a role in the sexual difference in the risk of HCC development through the regulation of OPN expression in patients with HCV.
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hamaoka
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Nagoshi
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Sugawara
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Naiki
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Inao
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan. smochida@saitama-med.ac.jp.|Yokohama Rosai Hospital, Labor Health and Welfare Organization, Yokohama, Japan. smochida@saitama-med.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochida
keywords: Hepatocellular carcinoma; Osteopontin; SNPs; SRY; Sex difference