Polymorphisms in interleukin-1B and its receptor antagonist genes and the risk of chronic obstructive pulmonary disease in a Korean population: a case-control study.
BACKGROUND
Although several studies have evaluated the association between interleukin-1B (IL1B) polymorphisms and the risk of chronic obstructive pulmonary disease (COPD), most of these studies have focused on -511C-->T and -31T-->C polymorphisms, and the results of these studies have been inconsistent. This study was conducted to investigate the association between four potentially functional polymorphisms of the IL1B gene (-3737C-->T, -1464G-->C, -511C-->T, and -31T-->C) and the risk of COPD. In addition, we examined a potential interaction of the IL1B polymorphisms with the VNTR polymorphism of the IL-1 receptor antagonist (IL1RN) gene in determining the risk of COPD.


METHODS
The IL1B and IL1RN genotypes were determined in 311 COPD patients and 386 healthy controls.


RESULTS
Individuals with at least one variant allele of the -511C-->T and -31T-->C polymorphisms were at a significantly increased risk for COPD when compared to carriers with each homozygous wild-type allele [adjusted odds ratio (OR) 1.53, 95% confidence interval (CI) 1.03-2.26, P=0.03; and adjusted OR 1.50, 95% CI 1.02-2.24, P=0.04, respectively]. When the COPD cases were stratified according to disease severity, the presence of at least one -511T and -31C alleles was significantly associated with severe COPD (adjusted OR 2.80, 95% CI 1.47-5.33, P=0.002; and adjusted OR 2.33, 95% CI 1.24-4.40, P=0.01, respectively), however, there was no significant association between the -511C-->T and -31T-->C genotypes and mild-to-moderate COPD. In addition, individuals carrying at least one IL1RN*2 allele were at a significantly lower risk for COPD compared to subjects carrying no IL1RN*2 allele (adjusted OR 0.51, 95% CI 0.26-0.98, P=0.04). In haplotype/diplotype analyses, individuals with one or two copies of the IL1B CCTC haplotype that carried the risk allele at all of the -3737C-->T, -1464G-->C, -511C-->T, and -31T-->C loci, were at a significantly increased risk of severe COPD when compared with subjects with zero copy of the CCTC haplotype (adjusted OR 1.96, 95% CI 1.16-3.29, P=0.01).


CONCLUSIONS
These findings suggest that polymorphisms in the IL1B and IL1RN genes might be useful markers for determining genetic susceptibility to COPD in a Korean population.
Lee
Jong Myung
JM
Department of Internal Medicine, Kyungpook National University Hospital, Samduk 2Ga 50, Daegu, 700-412, South Korea; Brain Korea 21, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu, South Korea.
Kang
Yeh Rim
YR
Park
Sun Ha
SH
Cha
Sung Ick
SI
Kim
Jong Sik
JS
Kang
Hyo Kyung
HK
Lee
Won Kee
WK
Kim
Min Jung
MJ
Kim
Chang Ho
CH
Kim
Nung Soo
NS
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D007723:Korea; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D012306:Risk
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta