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Relationship between microsatellite polymorphism in the haem oxygenase-1 gene promoter and longevity of the normal Japanese population
  1. M Yamaya1,
  2. K Nakayama1,
  3. S Ebihara1,
  4. H Hirai1,
  5. S Higuchi2,
  6. H Sasaki1
  1. 1Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan
  2. 2National Institute on Alcoholism, Kurihama National Hospital, 5-3-1 Nobi, Yokosuka, Kanagawa 239-0841, Japan
  1. Correspondence to:
 Dr H Sasaki, Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan;

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Oxidative stress is associated with the pathogenesis of various diseases such as cancer, pulmonary disease, and cardiovascular and cerebrovascular disease.1–3 In addition to environmental factors, genetic factors may be involved in determining a person’s susceptibility to diseases induced by oxidative stress. Although it is not obvious that these genotypes might be more frequent in older people, as the majority of the elderly are subject to age related disorders, healthy elderly people with some protective genetic background may escape from age related disorders and can reach an advanced age.

Haem oxygenase (HO) oxidatively degrades haem to biliverdin, which is subsequently reduced to bilirubin, an efficient scavenger of reactive oxygen species, by biliverdin reductase.4 Because not only HO-1, an inducible form of HO, but also a constitutive form of HO, including HO-2, provide cellular protection against haem and non-haem mediated oxidant injury,4 HO is suggested to have an important role in protection against various reactive oxygen species.

A (GT)n repeat of the rat prolactin gene is polymorphic, and this purine-pyrimidine alternating sequence, with Z conformation potential, negatively affects transcriptional activity in the rat prolactin gene.5 A (GT)n repeat of the human HO-1 gene is also polymorphic,6 and modulates human HO-1 gene transcription.7 We have shown that the large size (33≤ repeat) of a (GT)n repeat in the HO-1 gene (X14782) is associated with susceptibility to chronic pulmonary emphysema in Japanese populations and that a large (GT)n repeat categorised as a class L allele inhibits HO-1 gene transcription induced by hydrogen peroxide in cultured cell lines.8 Based on these findings, we hypothesised that the number of (GT)n repeats in the HO-1 gene is associated with susceptibility to the development of diseases induced by oxidative stress.

To test this hypothesis, we screened …

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