The effect of SERPINA1 mutations on α1-antitrypsin levels in COPD

Aims: Major mutations of SERPINA1, the gene encoding α1-antitrypsin (A1AT) are known to cause severe emphysema. Our study aimed to investigate the role of various heterozygotic mutations in modulating A1AT levels in COPD and control groups. Patients and methods: Blood samples (n=715) were collected from healthy non-smokers, healthy smokers, healthy ex-smokers, smokers with COPD, and ex-smokers with COPD. Clinical and respiratory parameters, A1AT levels, and low dose CT scans were evaluated. DNA was extracted, A1AT single nucleotide polymorphisms were determined for S, Z, M, 0 locations by SNP probes (Life Technologies) using Real-time PCR. Statistical analysis was performed by ANOVA tests and Spearman rank correlation. Results: A1AT levels were significantly higher in the COPD groups (1.47±0.24 g/L) compared to healthy smokers (1.37±0.2) or non-smokers (1.34±0.26)(p<0.001). There were no differences in the distribution of S, Z, M, 0 SNPs between groups. A1AT levels were inversely correlated to FEV1 in healthy smokers, ex-smokers with COPD. A1AT level in MZ and MS heterozygotes was significantly lower (0.87±0.1, 1.23±0.14, p<0,01) than MM groups (1.39±0.22), but FEV1/FVC was higher (75.6%±2.8) in MS group. A1AT levels in patients with emphysema seemed higher than those with no emphysema however only patients with mixed emphysema and bronchitis phenotype showed significant difference compared to patients with neither (1.6±0.28 vs1.43±0.22, p<0.05). Conclusions: Major A1AT mutations in heterozygotic form do not distinguish between patients with or without COPD. A1AT levels differ between clinically relevant COPD phenotypes. Further research is needed to clarify the role of A1AT in smoke-related pathologies.