Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers.
BACKGROUND
Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function. This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers. We evaluated the association between polymorphisms in ADAM33 gene with COPD and lung function in long term tobacco smokers.


METHODS
Caucasian subjects, at least 50 year old, who smoked >or= 20 pack-years (n = 880) were genotyped for 25 single nucleotide polymorphisms (SNPs) in ADAM33. COPD was defined as an FEV1/FVC ratio < 70% and percent-predicted (pp)FEV1 < 75% (n = 287). The control group had an FEV1/FVC ratio >or= 70% and ppFEV(1) >or= 80% (n = 311) despite >or= 20 pack years of smoking. Logistic and linear regressions were used for the analysis. Age, sex, and smoking status were considered as potential confounders.


RESULTS
Five SNPs in ADAM33 were associated with COPD (Q-1, intronic: p < 0.003; S1, Ile --> Val: p < 0.003; S2, Gly --> Gly: p < 0.04; V-1 intronic: p < 0.002; V4, in 3' untranslated region: p < 0.007). Q-1, S1 and V-1 were also associated with ppFEV1, FEV1/FVC ratio and ppFEF25-75 (p values 0.001 - 0.02). S2 was associated with FEV1/FVC ratio (p < 0.05). The association between S1 and residual volume revealed a trend toward significance (p value < 0.07). Linkage disequilibrium and haplotype analyses suggested that S1 had the strongest degree of association with COPD and pulmonary function abnormalities.


CONCLUSIONS
Five SNPs in ADAM33 were associated with COPD and lung function in long-term smokers. Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD.
Sadeghnejad
Alireza
A
Center for Human Genomics and Department of Medicine and Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. anejad@wfubmc.edu
Ohar
Jill A
JA
Zheng
Siqun L
SL
Sterling
David A
DA
Hawkins
Gregory A
GA
Meyers
Deborah A
DA
Bleecker
Eugene R
ER
D051722:ADAM Proteins / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014797:Vital Capacity; D044465:White People / Q000235:genetics
D051722:ADAM Proteins; C450441:ADAM33 protein, human