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Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers.

Sadeghnejad A, Ohar JA, Zheng SL, Sterling DA, Hawkins GA, Meyers DA, Bleecker ER - Respir. Res. (2009)

Bottom Line: Age, sex, and smoking status were considered as potential confounders.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Human Genomics and Department of Medicine and Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. anejad@wfubmc.edu

ABSTRACT

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.

Conclusion: 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.

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Haplotype analysis using a sliding window of three SNPs at a time for 19 SNPs with a MAF ≥ 5% in ADAM33 gene, having COPD as the phenotype of interest.
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Figure 2: Haplotype analysis using a sliding window of three SNPs at a time for 19 SNPs with a MAF ≥ 5% in ADAM33 gene, having COPD as the phenotype of interest.

Mentions: Haplotype analysis for the 19 SNPs with a MAF > 0.05 was performed using a sliding window to include 3 SNPs at a time. Haplotypes in three regions of the gene were significantly associated with COPD (Figure 2). The second and the third regions included SNPs that showed significance in individual SNP analysis (Q-1-S1-S2 and V-1-V4, respectively). Eight of the thirteen haplotypes were significantly associated with COPD included SNPs Q-1, S1 and S2. SNP S1 was present in six out of these eight SNPs. Linkage disequilibrium between the SNPs measured as D' and r2 are provided in supplemental materials (additional file 2 and additional file 3). In general, the correlation between SNPs was relatively low, but there were high LD measures between SNPs Q-1, S1 and S2 and V-1


Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers.

Sadeghnejad A, Ohar JA, Zheng SL, Sterling DA, Hawkins GA, Meyers DA, Bleecker ER - Respir. Res. (2009)

Haplotype analysis using a sliding window of three SNPs at a time for 19 SNPs with a MAF ≥ 5% in ADAM33 gene, having COPD as the phenotype of interest.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2664793&req=5

Figure 2: Haplotype analysis using a sliding window of three SNPs at a time for 19 SNPs with a MAF ≥ 5% in ADAM33 gene, having COPD as the phenotype of interest.
Mentions: Haplotype analysis for the 19 SNPs with a MAF > 0.05 was performed using a sliding window to include 3 SNPs at a time. Haplotypes in three regions of the gene were significantly associated with COPD (Figure 2). The second and the third regions included SNPs that showed significance in individual SNP analysis (Q-1-S1-S2 and V-1-V4, respectively). Eight of the thirteen haplotypes were significantly associated with COPD included SNPs Q-1, S1 and S2. SNP S1 was present in six out of these eight SNPs. Linkage disequilibrium between the SNPs measured as D' and r2 are provided in supplemental materials (additional file 2 and additional file 3). In general, the correlation between SNPs was relatively low, but there were high LD measures between SNPs Q-1, S1 and S2 and V-1

Bottom Line: Age, sex, and smoking status were considered as potential confounders.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Human Genomics and Department of Medicine and Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. anejad@wfubmc.edu

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus