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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2002-12-3733.
Submitted December 10, 2002
Accepted April 19, 2003
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, and Hidetada Sasaki*
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan
Department of Thoracic Surgery, IDAC, Tohoku University, Sendai, Japan
Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan
* Corresponding author; email: dept{at}geriat.med.tohoku.ac.jp.
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 postangioplasty restenosis. However, the biological 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 anti-apoptotic effects of HO-1, resulting in an association with susceptibility to oxidative stress-mediated diseases.
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