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

Alireza Sadeghnejad, Jill A. Ohar, Siqun L. Zheng, David Sterling, Gregory A. Hawkins, Deborah A. Meyers, Eugene R. Bleecker

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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 ≥ 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 ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 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.

Original languageEnglish
Article number21
JournalRespiratory Research
Volume10
DOIs
StatePublished - 12 Mar 2009

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Chronic Obstructive Pulmonary Disease
Tobacco
Lung
Single Nucleotide Polymorphism
Smoking
Residual Volume
Linkage Disequilibrium
3' Untranslated Regions
Haplotypes
Linear Models
Asthma
Logistic Models
Control Groups
Population
Genes

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Sadeghnejad, A., Ohar, J. A., Zheng, S. L., Sterling, D., Hawkins, G. A., Meyers, D. A., & Bleecker, E. R. (2009). Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers. Respiratory Research, 10, [21]. https://doi.org/10.1186/1465-9921-10-21
Sadeghnejad, Alireza ; Ohar, Jill A. ; Zheng, Siqun L. ; Sterling, David ; Hawkins, Gregory A. ; Meyers, Deborah A. ; Bleecker, Eugene R. / Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers. In: Respiratory Research. 2009 ; Vol. 10.
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title = "Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers",
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 ≥ 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 ≥ 70{\%} and ppFEV1 ≥ 80{\%} (n = 311) despite ≥ 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.",
author = "Alireza Sadeghnejad and Ohar, {Jill A.} and Zheng, {Siqun L.} and David Sterling and Hawkins, {Gregory A.} and Meyers, {Deborah A.} and Bleecker, {Eugene R.}",
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Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers. / Sadeghnejad, Alireza; Ohar, Jill A.; Zheng, Siqun L.; Sterling, David; Hawkins, Gregory A.; Meyers, Deborah A.; Bleecker, Eugene R.

In: Respiratory Research, Vol. 10, 21, 12.03.2009.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers

AU - Sadeghnejad, Alireza

AU - Ohar, Jill A.

AU - Zheng, Siqun L.

AU - Sterling, David

AU - Hawkins, Gregory A.

AU - Meyers, Deborah A.

AU - Bleecker, Eugene R.

PY - 2009/3/12

Y1 - 2009/3/12

N2 - 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 ≥ 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 ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 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.

AB - 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 ≥ 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 ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 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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U2 - 10.1186/1465-9921-10-21

DO - 10.1186/1465-9921-10-21

M3 - Article

VL - 10

JO - Respiratory Research

JF - Respiratory Research

SN - 1465-9921

M1 - 21

ER -