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Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency

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Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency

Content Provider	Springer Nature Link
Author	Topic, Aleksandra Nagorni Obradovic, Ljudmila Francuski, Djordje Ljujic, Mila Malic, Zivka Radojkovic, Dragica
Copyright 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.
Starting Page	746
Ending Page	752
Page Count	7
File Format	PDF
ISSN	00062928
Journal	Biochemical Genetics
Volume Number	54
Issue Number	5
e-ISSN	15734927
Language	English
Publisher	Springer US
Publisher Date	2016-06-06
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Oxidative stress Emphysema Alpha-1-antitrypsin deficiency Glutathione-S-transferase P1 Microsomal epoxide hydrolase Human Genetics Biochemistry Zoology Medical Microbiology
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Biochemistry Molecular Biology Ecology, Evolution, Behavior and Systematics

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Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency