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Association of susceptibility to the development of pneumonia in the older Japanese population with haem oxygenase-1 gene promoter polymorphism
  1. H Yasuda1,
  2. S Okinaga1,
  3. M Yamaya1,
  4. T Ohrui1,
  5. M Higuchi1,
  6. M Shinkawa1,
  7. S Itabashi1,
  8. K Nakayama1,
  9. M Asada1,
  10. A Kikuchi1,
  11. S Shibahara2,
  12. H Sasaki1
  1. 1Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan
  2. 2Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine
  1. Correspondence to:
 Dr Mutsuo Yamaya
 Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan; yamaya{at}geriat.med.tohoku.ac.jp

Abstract

Background: Oxidative stresses including cigarette smoking are implicated in the pathogenesis of cerebrovascular diseases, which are associated with pneumonia because of frequent aspiration. Haem oxygenase-1 (HO-1) acts in cytoprotection against oxidants, provides anti-inflammatory effects, and inhibits atherogenesis. A (GT)n dinucleotide repeat in the human HO-1 promoter modulates HO-1 gene expression and shows length polymorphism, which is grouped into three classes: class S (<27 repeats), class M (⩾27, <33 repeats), and class L (⩾33 repeats) alleles.

Objective: To investigate the correlation between the HO-1 gene polymorphism and development of pneumonia in elderly Japanese.

Methods: The length of the (GT)n repeats was analysed in 200 elderly patients with pneumonia and 200 control subjects. The association of the HO-1 gene polymorphism with risk of pneumonia was estimated by logistic regression.

Results: The proportion of allele frequencies in class L, and the proportion of genotypic frequencies in the L-allele carriers (L/L, L/M, and L/S), was significantly higher in patients with pneumonia than in controls (20% v 10% in class L, and 34% v 18% in L-allele carriers). After adjustment for potentially confounding factors, both cerebrovascular disorders and HO-1 gene L-allele carriers were significant and independent risk factors for pneumonia. The adjusted odds ratio for L-allele carriers v non-L-allele carrier was 2.1 (95% confidence interval, 1.2 to 3.6).

Conclusions: The large size of a (GT)n repeat in the HO-1 gene promoter may be associated with susceptibility to pneumonia in the older Japanese population.

  • COPD, chronic obstructive pulmonary disease
  • CPE, chronic pulmonary emphysema
  • HO, haem oxygenase
  • HO-1, inducible haem oxygenase
  • ROS, reactive oxygen species
  • TNF, tumour necrosis factor
  • pneumonia
  • haem oxygenase
  • gene polymorphism
  • cerebrovascular disease

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Footnotes

  • Conflicts of interest: none declared.

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