Estimating the Risk for Alpha-1 Antitrypsin Deficiency among COPD Patients: Evidence Supporting Targeted Screening

Center for the Evaluation of Risks to Human Reproduction, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA.
COPD Journal of Chronic Obstructive Pulmonary Disease (Impact Factor: 2.67). 09/2006; 3(3):133-9. DOI: 10.1080/15412550600829257
Source: PubMed


Alpha-1 antitrypsin deficiency is known as a significant genetic risk factor for COPD for carriers of phenotype PIMZ, and for phenotypes PIZZ and PISZ. Genetic epidemiological studies for alpha-1 antitrypsin deficiency conducted by others on both COPD patients and concurrent non-COPD controls were used to estimate the risk factors for all six phenotypic classes (namely, the normal phenotype PIMM, and the 5 deficiency allele phenotypes: PIMS, PIMZ, PISS, PISZ, and PIZZ). Studies on alpha-1 antitrypsin deficiency in white (Caucasian) COPD and non-COPD populations in 6 countries were combined to obtain estimates of the prevalence of the PIS and PIZ deficiency alleles in the combined COPD and non-COPD cohorts. The odds ratios for each of the six phenotypic classes of alpha-1 antitrypsin deficiency were calculated for a hypothetical population of 19.3 million white COPD patients in the United States of America. This approach demonstrated that 1,829,673 alpha-1 antitrypsin deficiency patients would be detected by testing 19.3 million white COPD patients and 536,033 in white non-COPD concurrent controls. The odds ratios for each of the phenotypic classes among white COPD patients demonstrate highly significant decreases in the normal phenotype PIMM, no significant change in the PIMS and PISS deficiency phenotypes, but highly significant increases in the prevalences of the PIMZ, PISZ, and PIZZ deficiency phenotypes. The result of the present study supports the concept of targeted screening for alpha-1 antitrypsin deficiency in countries with large populations of white (Caucasian) COPD patients.

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    • "To date, four genetic risk factors have been formally identified for COPD. Deficiency of α1 anti-trypsin (A1AT), an enzyme and a serum trypsin inhibitor that protects against protease remodelling in the airway, accounts for 2% of COPD in the population72, 73. Recently, genes for α-nicotinic acetylcholine receptor (CHRNA3/5)74, hedgehog-interacting protein (HHIP)75, 76 and iron regulatory protein 2 (IREB2)77–79 have been shown to be potential susceptibility loci for COPD. "
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