Intronic single-nucleotide polymorphisms in Bcl-2 are associated with chronic obstructive pulmonary disease severity.
OBJECTIVE
COPD is a multifactorial disease influenced by genetic and environmental factors, and gene-by-environmental interactions. There is considerable variability in the degree of airflow obstruction, moreover only 10-15% of chronic smokers develop COPD. These observations indicate that additional risk factors, possibly genetic, contribute to not only the susceptibility to COPD but also the development and severity of COPD. Recent paradigms highlight the presence and causal role of apoptosis in emphysema. There is a large amount of information on the genes involved in the regulation of apoptosis and one of the most studied is Bcl-2. The aim of this study was to investigate the genetic association of Bcl-2 gene with the level of lung function, that is, the severity, of COPD.


METHODS
The genetic association of Bcl-2 polymorphisms with lung function was investigated in 261 Japanese patients with COPD using 12 single-nucleotide polymorphisms (SNPs) in Bcl-2.


RESULTS
Four SNPs showed a significant association between the high and low lung function groups in a dominant trait comparison. Subsequent linkage-disequilibrium mapping and analyses of haplotype structure also showed a significant association between the level of lung function and two haplotypes comprised of the associated SNPs in Bcl-2.


CONCLUSIONS
Although the linkage between Bcl-2 gene and the susceptibility to COPD remains to be clarified, the findings of the current study indicate that Bcl-2 might be influencing the level of lung function, that is, the development and severity of COPD.
Sata
Makoto
M
Department of Cardiology, Pulmonology and Nephrology, Course of Internal Medicine and Therapeutics, Yamagata University School of Medicine, Yamagata, Japan. msata@hsp.ncvc.go.jp
Takabatake
Noriaki
N
Inoue
Sumito
S
Shibata
Yoko
Y
Abe
Shuichi
S
Machiya
Jun-ichi
J
Wada
Toshihiro
T
Ji
Guijin
G
Kido
Takashi
T
Matsuura
Tadashi
T
Muramatsu
Masa-aki
MA
Kubota
Isao
I
D000368:Aged; D004247:DNA / Q000235:genetics*; D005541:Forced Expiratory Volume / Q000502:physiology; D019254:Genes, bcl-2 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology; D012189:Retrospective Studies; D012720:Severity of Illness Index
D004247:DNA