α1-antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts

Inga Cecilie Sørheim, Per Bakke, Amund Gulsvik, Sreekumar G. Pillai, Ane Johannessen, Per I. Gaarder, Edward J. Campbell, Alvar Agustí, Peter M.A. Calverley, Claudio F. Donner, Barry J. Make, Stephen I. Rennard, Jørgen Vestbo, Emiel F.M. Wouters, Peter D. Paré, Robert D. Levy, Harvey O. Coxson, David A. Lomas, Craig P. Hersh, Edwin K. Silverman

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Abstract

Background: Severe α1 -antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1- antitrypsin, but whether they have an increased risk of COPD is uncertain. Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. Results: PI MZ was associated with a 3.5% lower FEV1/FVC ratio in the case-control study (P =.035) and 3.9% lower FEV1/vital capacity (VC) ratio in the family study(P =.009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans(P =.003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.

Original languageEnglish (US)
Pages (from-to)1125-1132
Number of pages8
JournalChest
Volume138
Issue number5
DOIs
StatePublished - Nov 1 2010

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Protease Inhibitors
Emphysema
Chronic Obstructive Pulmonary Disease
Case-Control Studies
Vital Capacity
Thorax
Norway
Heterozygote
North America
Population
Smoking
Phenotype

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Sørheim, I. C., Bakke, P., Gulsvik, A., Pillai, S. G., Johannessen, A., Gaarder, P. I., ... Silverman, E. K. (2010). α1-antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts. Chest, 138(5), 1125-1132. https://doi.org/10.1378/chest.10-0746

α1-antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts. / Sørheim, Inga Cecilie; Bakke, Per; Gulsvik, Amund; Pillai, Sreekumar G.; Johannessen, Ane; Gaarder, Per I.; Campbell, Edward J.; Agustí, Alvar; Calverley, Peter M.A.; Donner, Claudio F.; Make, Barry J.; Rennard, Stephen I.; Vestbo, Jørgen; Wouters, Emiel F.M.; Paré, Peter D.; Levy, Robert D.; Coxson, Harvey O.; Lomas, David A.; Hersh, Craig P.; Silverman, Edwin K.

In: Chest, Vol. 138, No. 5, 01.11.2010, p. 1125-1132.

Research output: Contribution to journalArticle

Sørheim, IC, Bakke, P, Gulsvik, A, Pillai, SG, Johannessen, A, Gaarder, PI, Campbell, EJ, Agustí, A, Calverley, PMA, Donner, CF, Make, BJ, Rennard, SI, Vestbo, J, Wouters, EFM, Paré, PD, Levy, RD, Coxson, HO, Lomas, DA, Hersh, CP & Silverman, EK 2010, 'α1-antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts', Chest, vol. 138, no. 5, pp. 1125-1132. https://doi.org/10.1378/chest.10-0746
Sørheim IC, Bakke P, Gulsvik A, Pillai SG, Johannessen A, Gaarder PI et al. α1-antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts. Chest. 2010 Nov 1;138(5):1125-1132. https://doi.org/10.1378/chest.10-0746
Sørheim, Inga Cecilie ; Bakke, Per ; Gulsvik, Amund ; Pillai, Sreekumar G. ; Johannessen, Ane ; Gaarder, Per I. ; Campbell, Edward J. ; Agustí, Alvar ; Calverley, Peter M.A. ; Donner, Claudio F. ; Make, Barry J. ; Rennard, Stephen I. ; Vestbo, Jørgen ; Wouters, Emiel F.M. ; Paré, Peter D. ; Levy, Robert D. ; Coxson, Harvey O. ; Lomas, David A. ; Hersh, Craig P. ; Silverman, Edwin K. / α1-antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts. In: Chest. 2010 ; Vol. 138, No. 5. pp. 1125-1132.
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abstract = "Background: Severe α1 -antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1- antitrypsin, but whether they have an increased risk of COPD is uncertain. Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. Results: PI MZ was associated with a 3.5{\%} lower FEV1/FVC ratio in the case-control study (P =.035) and 3.9{\%} lower FEV1/vital capacity (VC) ratio in the family study(P =.009). In the case-control study, PI MZ also was associated with 3.7{\%} more emphysema on quantitative analysis of chest CT scans(P =.003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.",
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T1 - α1-antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts

AU - Sørheim, Inga Cecilie

AU - Bakke, Per

AU - Gulsvik, Amund

AU - Pillai, Sreekumar G.

AU - Johannessen, Ane

AU - Gaarder, Per I.

AU - Campbell, Edward J.

AU - Agustí, Alvar

AU - Calverley, Peter M.A.

AU - Donner, Claudio F.

AU - Make, Barry J.

AU - Rennard, Stephen I.

AU - Vestbo, Jørgen

AU - Wouters, Emiel F.M.

AU - Paré, Peter D.

AU - Levy, Robert D.

AU - Coxson, Harvey O.

AU - Lomas, David A.

AU - Hersh, Craig P.

AU - Silverman, Edwin K.

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Background: Severe α1 -antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1- antitrypsin, but whether they have an increased risk of COPD is uncertain. Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. Results: PI MZ was associated with a 3.5% lower FEV1/FVC ratio in the case-control study (P =.035) and 3.9% lower FEV1/vital capacity (VC) ratio in the family study(P =.009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans(P =.003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.

AB - Background: Severe α1 -antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1- antitrypsin, but whether they have an increased risk of COPD is uncertain. Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. Results: PI MZ was associated with a 3.5% lower FEV1/FVC ratio in the case-control study (P =.035) and 3.9% lower FEV1/vital capacity (VC) ratio in the family study(P =.009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans(P =.003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.

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