Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency.
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.
Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe, 450, Belgrade, 11221, Serbia. aleksandra.topic1@gmail.com.
Aleksandra
A
Topic
School of Medicine, Clinic for Pulmonary Diseases Clinical Centre of Serbia, University of Belgrade, Belgrade, Serbia.
Ljudmila
L
Nagorni-Obradovic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Djordje
D
Francuski
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Mila
M
Ljujic
Faculty of Pharmacy, University of Bijeljina, Bijeljina, Bosnia and Herzegovina.
Zivka
Z
Malic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Dragica
D
Radojkovic
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000328:Adult; D017668:Age of Onset; D002097:C-Reactive Protein / Q000378:metabolism*; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018384:Oxidative Stress; D011379:Prognosis; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics* / Q000652:urine
D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi
Alpha-1-antitrypsin deficiency; Emphysema; Glutathione-S-transferase P1; Microsomal epoxide hydrolase; Oxidative stress