Microsatellite polymorphism in heme oxygenase-1 gene promoter is associated with susceptibility to oxidant-induced apoptosis in lymphoblastoid cell lines

Hisao Hirai, Hiroshi Kubo, Mutsuo Yamaya, Katsutoshi Nakayama, Muneo Numasaki, Seiichi Kobayashi, Satoshi Suzuki, Shigeki Shibahara, Hidetada Sasaki

Research output: Contribution to journalArticlepeer-review

138 Citations (Scopus)

Abstract

Heme oxygenase-1 (HO-1) confers cytoprotection against oxidative stress. A (GT)n dinucleotide repeat in the 5′-flanking region of human HO-1 gene shows length polymorphism, which was classified into S (< 27 GT), M (27-32 GT), and L alleles (≥ 33 GT). Polymorphism in the HO-1 gene promoter was shown to be associated with susceptibility to pulmonary emphysema and restenosis after angioplasty. However, the biologic mechanism underlying these associations is still unclear. To examine this issue, we established lymphoblastoid cell lines (LCLs) from subjects possessing S/S or L/L genotypes. HO-1 mRNA expressions and HO activities induced by oxidative stress were significantly higher in LCLs with S/S than those with L/L. Furthermore, LCLs with S/S were significantly more resistant to oxidant-induced apoptosis than those with L/L. These findings suggested that the polymorphism of the HO-1 gene is associated with the strength of antiapoptotic effects of HO-1, resulting in an association with susceptibility to oxidative stress-mediated diseases.

Original languageEnglish
Pages (from-to)1619-1621
Number of pages3
JournalBlood
Volume102
Issue number5
DOIs
Publication statusPublished - 2003 Sep 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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