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GPX3 rs8177412 Polymorphism Modifies Risk of Upper Urothelial Tumors in Patients with Balkan Endemic Nephropathy.

التفاصيل البيبلوغرافية
العنوان: GPX3 rs8177412 Polymorphism Modifies Risk of Upper Urothelial Tumors in Patients with Balkan Endemic Nephropathy.
المؤلفون: Radic Savic Z; Department of Medical Biochemistry, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina.; Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina., Coric V; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.; Center of Excellence for Redox Medicine, Biotech Place, 2W-017, 575 North Patterson Avenue, Winston-Salem, NC 27157, USA., Vidovic S; Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina.; Department of Human Genetics, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina., Vidovic V; Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina.; Department of Human Genetics, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina., Becarevic J; Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina., Milovac I; Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina.; Department of Human Genetics, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina., Reljic Z; Medical Laboratory 'PAN LAB', 36000 Kraljevo, Serbia., Mirjanic-Azaric B; Department of Medical Biochemistry, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina., Skrbic R; Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina.; Academy of Sciences and Arts of the Republic of Srpska, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina., Gajanin R; Department of Pathological Anatomy, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina., Matic M; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.; Center of Excellence for Redox Medicine, Biotech Place, 2W-017, 575 North Patterson Avenue, Winston-Salem, NC 27157, USA., Simic T; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.; Center of Excellence for Redox Medicine, Biotech Place, 2W-017, 575 North Patterson Avenue, Winston-Salem, NC 27157, USA.; Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia.
المصدر: Medicina (Kaunas, Lithuania) [Medicina (Kaunas)] 2023 Aug 04; Vol. 59 (8). Date of Electronic Publication: 2023 Aug 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 9425208 Publication Model: Electronic Cited Medium: Internet ISSN: 1648-9144 (Electronic) Linking ISSN: 1010660X NLM ISO Abbreviation: Medicina (Kaunas) Subsets: MEDLINE
أسماء مطبوعة: Publication: 2018- : Basel, Switzerland : MDPI
Original Publication: Kaunas : Lietuvos gydytojų sąjunga
مواضيع طبية MeSH: Urinary Bladder Neoplasms*/genetics , Carcinoma, Transitional Cell* , Balkan Nephropathy*/genetics , Kidney Diseases*, Humans ; Female ; Kelch-Like ECH-Associated Protein 1 ; NF-E2-Related Factor 2 ; Glutathione Peroxidase/genetics
مستخلص: Current data suggest that aristolochic acid (AA) exposure is a putative cause of Balkan endemic nephropathy (BEN), a chronic kidney disease strongly associated with upper tract urothelial carcinoma. The cellular metabolism of AA is associated with the production of reactive oxygen species, resulting in oxidative distress. Purpose: Therefore, the aim of this study was to analyze individual, combined and cumulative effect of antioxidant gene polymorphisms ( Nrf2 rs6721961, KEAP1 rs1048290, GSTP1AB rs1695, GSTP1CD rs1138272, GPX3 rs8177412 and MDR1 rs1045642), as well as GSTP1ABCD haplotypes with the risk for BEN development and associated urothelial cell carcinoma in 209 BEN patients and 140 controls from endemic areas. Experimental method: Genotyping was performed using polymerase chain reaction (PCR) and PCR with confronting two-pair primers (PCR-CTTP) methods. Results: We found that female patients carrying both variant GPX3 rs8177412 and MDR1 rs1045642 genotypes in combination exhibited significant risk towards BEN (OR 1 = 3.34, 95% CI = 1.16-9.60, p = 0.025; OR 2 = 3.79, 95% CI = 1.27-11.24, p = 0.016). Moreover, significant association was determined between GPX3 rs8174412 polymorphism and risk for urothelial carcinoma. Carriers of variant GPX3 *TC + CC genotype were at eight-fold increased risk of BEN-associated urothelial tumors development. There was no individual or combined impact on BEN development and BEN-associated tumors among all examined polymorphisms. The haplotype consisting of variant alleles for both polymorphisms G and T was associated with 1.6-fold increased risk although statistically insignificant (OR = 1.64; 95% CI = 0.75-3.58; p = 0.21). Conclusions: Regarding GPX3 rs8177412 polymorphism, the gene variant that confers lower expression is associated with significant increase in upper urothelial carcinoma risk. Therefore, BEN patients carrying variant GPX3 genotype should be more frequently monitored for possible upper tract urothelial carcinoma development.
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معلومات مُعتمدة: 451-03-47/2023-01/200110 Ministry of Science, Technological Development and Innovation of the Republic of Serbia
فهرسة مساهمة: Keywords: Balkan endemic nephropathy; GPX3 polymorphism; aristolochic acid; upper tract urothelial cell carcinoma
المشرفين على المادة: 0 (Kelch-Like ECH-Associated Protein 1)
0 (NF-E2-Related Factor 2)
94218WFP5T (aristolochic acid I)
EC 1.11.1.- (GPX3 protein, human)
EC 1.11.1.9 (Glutathione Peroxidase)
تواريخ الأحداث: Date Created: 20230826 Date Completed: 20230828 Latest Revision: 20230829
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10456338
DOI: 10.3390/medicina59081421
PMID: 37629712
قاعدة البيانات: MEDLINE
الوصف
تدمد:1648-9144
DOI:10.3390/medicina59081421