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Chest. 2010 Nov;138(5):1125-32. doi: 10.1378/chest.10-0746. Epub 2010 Jul 1.

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

Author information

  • 1Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA.

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.

PMID:
20595457
[PubMed - indexed for MEDLINE]
PMCID:
PMC2972629
Free PMC Article

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