Associations of Alpha-1 antitrypsin Pi*S allele with COPD

Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive airflow limitation and related to an abnormal inflammatory response of the lung that results from a gene-environment interaction. The best documented genetic risk factor is severe hereditary deficiency of Alpha-1 antitrypsin (AAT). The presence of PiZ allele (Glu342→ Lys) in homozygote state, that is inherited in autosomal recessive way is already well proven factor for developing COPD. Data about PiS allele (Glu264→ Val) influence for developing COPD are not ascertain yet. Current study analyzed 1000 COPD patients, that clinical diagnosis was confirmed by using GOLD spirometric criteria. AAT serum concentrations were measured by means of nephelometry, and phenotyping was carried out by means of isoelectic-focusing. We found PiS allele in 44 patients: 1 in homozygous state SS, 43 in heterozygous state: 40 MS and 3 SZ. AAT concentrations were significantly lower in SS and SZ group compared with normal AAT variant MM (p= 0,035). Lung function parameter - forced expiratory volume in one second (FEV1) was also worse in SS and SZ patients (p=0,043) than in MM group. Clinical and biochemical characteristics of COPD patients with MS and MM phenotypes has no statistical differences. In conclusion, the results of the present study support the concept that PiS allele is genetic risk factor for COPD for carriers of phenotypes SS and SZ, but not SM.