Background: Severe -antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of -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 Kamagra shop, go now.
Results: PI MZ was associated with a 3.5% lower FEV/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 FEV/(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.
Abbreviations: AAT = cq-antitrypsin; BD = bronchodilator; FEV1/(F)VC = FEV/FVC or FEV/vital capacity ratios; HU = Hounsfield units; ICGN = International COPD Genetics Network; %LAA950 = percent low attenuation areas <-950 Hounsfield units; PI = protease inhibitor; SRWA-Pi10 = square root of wall area at internal perimeter of 10 mm; VC = vital capacity.
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Severe a antitrypsin (AAT) deficiency is a known genetic risk factor for COPD, but severe deficiency only accounts for about 1% to 2% of all COPD cases. AAT is a protease inhibitor (PI) encoded by the SERPINA1 locus on chromosome 14q32.1. The main function of AAT is to protect the lung tissue against proteolytic stress, primarily by inactivation of the enzyme neutrophil elastase. More than 100 alleles at the PI locus have been described, most of them quite rare.