Microsatellite polymorphism in heme oxygenase-1 gene promoter is associated with susceptibility to oxidant-induced apoptosis in lymphoblastoid cell lines.
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.
Hirai
Hisao
H
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Kubo
Hiroshi
H
Yamaya
Mutsuo
M
Nakayama
Katsutoshi
K
Numasaki
Muneo
M
Kobayashi
Seiichi
S
Suzuki
Satoshi
S
Shibahara
Shigeki
S
Sasaki
Hidetada
H
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D005260:Female; D020022:Genetic Predisposition to Disease; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D018895:Microsatellite Repeats; D008875:Middle Aged; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
D008565:Membrane Proteins; D016877:Oxidants; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1