Association of susceptibility to the development of pneumonia in the older Japanese population with haem oxygenase-1 gene promoter polymorphism.
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 (> or = 27, <33 repeats), and class L (> or = 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.
Yasuda
H
H
Okinaga
S
S
Yamaya
M
M
Ohrui
T
T
Higuchi
M
M
Shinkawa
M
M
Itabashi
S
S
Nakayama
K
K
Asada
M
M
Kikuchi
A
A
Shibahara
S
S
Sasaki
H
H
D000368:Aged; D044466:Asian People / Q000235:genetics*; D002263:Carboxyhemoglobin / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D011014:Pneumonia / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D002263:Carboxyhemoglobin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1