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 -