ELECTRONIC LETTER

Association of susceptibility to the development of pneumonia in the older Japanese population with haem oxygenase-1 gene promoter polymorphism

H Yasuda¹, S Okinaga¹, M Yamaya¹, T Ohrui¹, M Higuchi¹, M Shinkawa¹, S Itabashi¹, K Nakayama¹, M Asada¹, A Kikuchi¹, S Shibahara², H Sasaki¹

¹ Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan
² Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine

Correspondence to:
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

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.

Abbreviations: 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

Keywords: pneumonia; haem oxygenase; gene polymorphism; cerebrovascular disease

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Mizgerd, J. P. (2008). Acute Lower Respiratory Tract Infection. NEJM 358: 716-727 [Full Text]  
• Fredenburgh, L. E., Perrella, M. A., Mitsialis, S. A. (2007). The Role of Heme Oxygenase-1 in Pulmonary Disease. Am. J. Respir. Cell Mol. Bio. 36: 158-165 [Abstract] [Full Text]