Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency
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2016
Authors
Topić, AleksandraNagorni-Obradović, Ljudmila
Francuski, Djordje
Ljujić, Mila
Malić, Zivka
Radojković, Dragica
Article (Published version)
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Show full item recordAbstract
Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory ...and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.
Keywords:
Oxidative stress / Microsomal epoxide hydrolase / Glutathione-S-transferase P1 / Emphysema / Alpha-1-antitrypsin deficiencySource:
Biochemical Genetics, 2016, 54, 5, 746-752Publisher:
- Springer/Plenum Publishers, New York
Funding / projects:
- Complex diseases as a model system for phenotype modulation- structural and functional analysis of molecular biomarkers (RS-MESTD-Basic Research (BR or ON)-173008)
DOI: 10.1007/s10528-016-9748-7
ISSN: 0006-2928
PubMed: 27271084
WoS: 000383038400013
Scopus: 2-s2.0-84986551099
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Topić, Aleksandra AU - Nagorni-Obradović, Ljudmila AU - Francuski, Djordje AU - Ljujić, Mila AU - Malić, Zivka AU - Radojković, Dragica PY - 2016 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/900 AB - Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients. PB - Springer/Plenum Publishers, New York T2 - Biochemical Genetics T1 - Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency EP - 752 IS - 5 SP - 746 VL - 54 DO - 10.1007/s10528-016-9748-7 ER -
@article{ author = "Topić, Aleksandra and Nagorni-Obradović, Ljudmila and Francuski, Djordje and Ljujić, Mila and Malić, Zivka and Radojković, Dragica", year = "2016", abstract = "Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.", publisher = "Springer/Plenum Publishers, New York", journal = "Biochemical Genetics", title = "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency", pages = "752-746", number = "5", volume = "54", doi = "10.1007/s10528-016-9748-7" }
Topić, A., Nagorni-Obradović, L., Francuski, D., Ljujić, M., Malić, Z.,& Radojković, D.. (2016). Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics Springer/Plenum Publishers, New York., 54(5), 746-752. https://doi.org/10.1007/s10528-016-9748-7
Topić A, Nagorni-Obradović L, Francuski D, Ljujić M, Malić Z, Radojković D. Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics. 2016;54(5):746-752. doi:10.1007/s10528-016-9748-7 .
Topić, Aleksandra, Nagorni-Obradović, Ljudmila, Francuski, Djordje, Ljujić, Mila, Malić, Zivka, Radojković, Dragica, "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency" in Biochemical Genetics, 54, no. 5 (2016):746-752, https://doi.org/10.1007/s10528-016-9748-7 . .