Polymorphisms in promoter sequences of the p15 ( INK4B ) and PTEN genes of normal Japanese individuals

Biochem Genet. 2010 Dec;48(11-12):970-86. doi: 10.1007/s10528-010-9379-3. Epub 2010 Sep 23.


Gene promoter regions of p15(INK4B), a cyclin-dependent kinase inhibitor, and phosphatase and tensin homolog (PTEN), a dual-function protein and lipid phosphatase, interact with regulatory factors for gene transcription and methylation. Normal individuals exhibit sequence polymorphisms in these regulatory genes. We isolated genomic DNA from whole blood of healthy Japanese individuals and sequenced promoter regions of the p15 ( INK4B ) and PTEN genes. We also examined the influence of polymorphisms on promoter activity in several cell lines. We identified polymorphisms at positions -699, -394, and -242 and an insertion at position -320 in the p15 ( INK4B ) gene and a polymorphism at position -1142 in the PTEN gene. Reporter gene analysis revealed that these polymorphisms influenced transcriptional regulation in their cell lines. Our results indicate for the first time that promoter sequences of the p15 ( INK4B ) and PTEN genes differ among normal Japanese individuals and that promoter polymorphisms can influence gene transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence / genetics
  • Cell Line, Transformed / chemistry
  • Cyclin-Dependent Kinase Inhibitor p15 / blood
  • Cyclin-Dependent Kinase Inhibitor p15 / chemistry
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p15 / metabolism*
  • DNA / blood
  • DNA / genetics
  • Gene Expression Regulation*
  • Genes, Reporter
  • Humans
  • Japan
  • Luciferases / analysis
  • Molecular Sequence Data
  • Mutation / genetics
  • PTEN Phosphohydrolase / blood
  • PTEN Phosphohydrolase / chemistry
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Transcription Factors / metabolism


  • Cyclin-Dependent Kinase Inhibitor p15
  • Transcription Factors
  • DNA
  • Luciferases
  • PTEN Phosphohydrolase
  • PTEN protein, human