Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD)

Abstract

Alpha-1-antitrypsin (AAT) plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD). In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val), PiM2 (Arg101His), PiM3 (Glu376Asp), PiS (Glu264Val) and PiZ (Glu342Lys) SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3) and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms.

Gene polymorphisms and chronic obstructive pulmonary disease

“…Eleven SNPs of the genes encoding IL‐10 and the alpha subunit of its receptor (IL10RA) were not associated with the rate of decline in FEV1 in smoking‐induced COPD . Carriers of tested polymorphisms (PIM1, PIM2, PIM3, PIS and PIZ) of Alpha‐1 antitrypsin gene were not associated with the annual decline of FEV1 determined for 2 years in a Tunisian study .…”

“…A meta‐analysis including 16 case–control studies and cross‐sectional studies demonstrated that patients with PI MZ had higher risk to suffer from COPD as compared with those with PI MM homozygotes , while another meta‐analysis found that individuals with PI SZ heterozygotes had significantly higher risk for COPD . Another study on SERPINA1 alleles of M1, PI M2, PI M3, PI S and PI Z found no significant differences in allele frequencies between COPD patients and healthy controls . Further studies are needed with enough cases to confirm the role of those gene homozygotes in the risk of COPD.…”

“…There are also negative results concerning the relationship between gene polymorphisms and COPD‐related phenotypes. For example, a cross‐sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PIM1, PIM2, PIM3) and the emphysematous type of COPD .…”

The effect of α1-antitrypsin deficiency combined with increased bacterial loads on chronic obstructive pulmonary disease pharmacotherapy: A prospective, parallel, controlled pilot study

“…DNA samples with the Pi∗M were cut into 78- and 20-bp bands, but the Pi∗S remained as a 98-bp band. While for the Z-variant (Pi∗MZ, Pi∗ZZ), the previously described Hyp99I/amplified fragment length polymorphism (AFLP) method was adopted [31]. Exon V was amplified using the primer pair (IDT DNA) 5M (5′-GAGCCTTGCTCGAGGCCTGGGATC-3′), and 5P (5′-CAGGAAAACATGGGAGGGATTTAC-′3).…”

Interactions between single nucleotide polymorphism of <em>SERPINA1</em> gene and smoking in association with COPD: a case&ndash;control study

“…A null mutation of SERPINA1 gene was shown to significantly increase the risk of severe emphysema 2. Single nucleotide polymorphisms (SNPs) of SERPINA1 have also linked to a heightened susceptibility to COPD 3,4. However, majority of these studies were performed in Caucasians, definitive evidence of such an association is yet to be demonstrated in Asian population 5,6…”