TY - JOUR
T1 - The protease inhibitor PI*S allele and COPD
T2 - a meta-analysis
AU - Hersh, C P
AU - Ly, N P
AU - Berkey, C S
AU - Silverman, E K
AU - Nordestgaard, B G
AU - Dahl, Morten
AU - Dahl, M
PY - 2005/7
Y1 - 2005/7
N2 - In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting for smoking. Furthermore, mean forced expiratory volume in one second, a measure of airflow obstruction and a defining feature of COPD, did not differ between PI MS and PI MM individuals. There were not enough cases to summarise the risk of COPD in PI SS homozygotes. In conclusion, the results show that the PI SZ genotype is a significant risk factor for chronic obstructive pulmonary disease. The risk of chronic obstructive pulmonary disease due to the PI MS genotype is not substantially elevated.
AB - In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting for smoking. Furthermore, mean forced expiratory volume in one second, a measure of airflow obstruction and a defining feature of COPD, did not differ between PI MS and PI MM individuals. There were not enough cases to summarise the risk of COPD in PI SS homozygotes. In conclusion, the results show that the PI SZ genotype is a significant risk factor for chronic obstructive pulmonary disease. The risk of chronic obstructive pulmonary disease due to the PI MS genotype is not substantially elevated.
KW - Alleles
KW - Case-Control Studies
KW - Confidence Intervals
KW - Cross-Sectional Studies
KW - Female
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Heterozygote
KW - Humans
KW - Male
KW - Mutation
KW - Odds Ratio
KW - Pulmonary Disease, Chronic Obstructive
KW - Respiratory Function Tests
KW - Sensitivity and Specificity
KW - Serine Proteinase Inhibitors
KW - Severity of Illness Index
KW - alpha 1-Antitrypsin Deficiency
U2 - 10.1183/09031936.05.00135704
DO - 10.1183/09031936.05.00135704
M3 - Journal article
C2 - 15994391
VL - 26
SP - 67
EP - 76
JO - The European Respiratory Journal
JF - The European Respiratory Journal
SN - 0903-1936
IS - 1
ER -