Polymorphism of alpha-1-antitrypsin in hematological malignancies
Abstract
Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (chi(2) = 4.42, d.f. 11, p = 0.96 and chi(2) = 4.71, d.f. 11, p = 0.97, ...respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant.
Keywords:
Alpha-1-antitrypsin / polymorphism / lymphomasSource:
Genetics and Molecular Biology, 2009, 32, 4, 716-719Publisher:
- Soc Brasil Genetica, Ribeirao Pret
Funding / projects:
- Istraživanje dejstava modifikatora biološkog odgovora u fiziološkim i patološkim stanjima (RS-145006)
DOI: 10.1590/S1415-47572009005000085
ISSN: 1415-4757
PubMed: 21637443
WoS: 000272182700008
Scopus: 2-s2.0-73449134104
Collections
Institution/Community
PharmacyTY - JOUR AU - Topić, Aleksandra AU - Juranić, Zorica AU - Jelic, Svetislav AU - Golubicič-Magazinovic, Ivana PY - 2009 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1208 AB - Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (chi(2) = 4.42, d.f. 11, p = 0.96 and chi(2) = 4.71, d.f. 11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant. PB - Soc Brasil Genetica, Ribeirao Pret T2 - Genetics and Molecular Biology T1 - Polymorphism of alpha-1-antitrypsin in hematological malignancies VL - 32 IS - 4 SP - 716 EP - 719 DO - 10.1590/S1415-47572009005000085 ER -
@article{ author = "Topić, Aleksandra and Juranić, Zorica and Jelic, Svetislav and Golubicič-Magazinovic, Ivana", year = "2009", abstract = "Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (chi(2) = 4.42, d.f. 11, p = 0.96 and chi(2) = 4.71, d.f. 11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant.", publisher = "Soc Brasil Genetica, Ribeirao Pret", journal = "Genetics and Molecular Biology", title = "Polymorphism of alpha-1-antitrypsin in hematological malignancies", volume = "32", number = "4", pages = "716-719", doi = "10.1590/S1415-47572009005000085" }
Topić, A., Juranić, Z., Jelic, S.,& Golubicič-Magazinovic, I.. (2009). Polymorphism of alpha-1-antitrypsin in hematological malignancies. in Genetics and Molecular Biology Soc Brasil Genetica, Ribeirao Pret., 32(4), 716-719. https://doi.org/10.1590/S1415-47572009005000085
Topić A, Juranić Z, Jelic S, Golubicič-Magazinovic I. Polymorphism of alpha-1-antitrypsin in hematological malignancies. in Genetics and Molecular Biology. 2009;32(4):716-719. doi:10.1590/S1415-47572009005000085 .
Topić, Aleksandra, Juranić, Zorica, Jelic, Svetislav, Golubicič-Magazinovic, Ivana, "Polymorphism of alpha-1-antitrypsin in hematological malignancies" in Genetics and Molecular Biology, 32, no. 4 (2009):716-719, https://doi.org/10.1590/S1415-47572009005000085 . .