Εξορθολογισμός της φαρμακευτικής χορήγησης χλωροκίνης και ρασμπουρικάσης σε ασθενείς με ανεπάρκεια του ενζύμου G6PD
Keywords:
2MoBiL, φορητό εργαστήριο μοριακής βιολογίας, G6PD, ανεπάρκεια ενζύμου G6PD, χλωροκίνη, ρασμπουρικάση, γονοτύπηση
Abstract
Η ανεπάρκεια του ενζύμου αφυδρογονάση της 6-φωσφορικής γλυκόζης (G6PD) εντοπίζεται με αυξημένη συχνότητα στη Ελλάδα. Το υπεύθυνο γονίδιο είναι φυλοσύνδετο, και ένα αλληλόμορφο του πολυμορφισμού rs5030868 συσχετίζεται με την ανεπάρκεια κατηγορίας ΙΙ του G6PD που ενέχει κίνδυνο αιμολυτικής αναιμίας κατά τη λήψη των φαρμάκων χλωροκίνη και ρασμπουρικάση με φαρμακογονιδιωματικές συσχετίσεις επίπεδου 3 και 1Α αντίστοιχα. Μια γρήγορη, εύκολη, αξιόπιστη και οικονομική μέθοδος γονοτύπησης του πολυμορφικού τόπου rs5030868 με φαινολική εκχύλιση DNA και αλληλοειδική γονοτύπηση τεσσάρων εκκινητών με PCR σε φορητό εργαστήριο μοριακής βιολογίας αναπτύχθηκε για να επιτρέπει τη βελτιστοποίηση χορήγησης της χλωροκίνης και της ρασμπουρικάσης ειδικά σε ασθενείς με νόσο CoViD-19 σε περιόδους κρίσης. Η μέθοδος συγκρίθηκε με γονοτύπηση μέσω αλληλούχισης κατά Sanger και με ταυτόσημες PCR σε εδραίο θερμικό κυκλοποιητή και αποδείχθηκε αξιόπιστη με τιμή p >.5 στη δοκιμή κατά Fisher.
References
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2. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19 [Internet]. Vol. 55, International Journal of Antimicrobial Agents. Elsevier B.V.; 2020 [cited 2020 Sep 7]. Available from: https://pubmed.ncbi.nlm.nih.gov/32145363/ .
3. Capoluongo ED, Capoluongo ED, Capoluongo ED, Amato F, Amato F, Castaldo G, et al. The friendly use of chloroquine in the COVID-19 disease: A warning for the G6PD-deficient males and for the unaware carriers of pathogenic alterations of the G6PD gene [Internet]. Vol. 58, Clinical Chemistry and Laboratory Medicine. De Gruyter; 2020 [cited 2020 Sep 7]. p. 1162–4. Available from: https://pubmed.ncbi.nlm.nih.gov/32333649/
4. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis [Internet]. 2020 Jul 28 [cited 2020 Sep 7];71(15):732–9. Available from: https://pubmed.ncbi.nlm.nih.gov/32150618/
5. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19 [Internet]. Vol. 55, International Journal of Antimicrobial Agents. Elsevier B.V.; 2020 [cited 2020 Sep 7]. Available from: https://pubmed.ncbi.nlm.nih.gov/32145363/ .
6. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents [Internet]. 2020 Jul 1 [cited 2020 Sep 7];56(1). Available from: https://pubmed.ncbi.nlm.nih.gov/32205204/
7. Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro [Internet]. Vol. 6, Cell Discovery. Springer Nature; 2020 [cited 2020 Sep 7]. Available from: https://pubmed.ncbi.nlm.nih.gov/32194981/
8. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro [Internet]. Vol. 30, Cell Research. Springer Nature; 2020 [cited 2020 Sep 7]. p. 269–71. Available from: https://pubmed.ncbi.nlm.nih.gov/32020029/
9. Touret F, de Lamballerie X. Of chloroquine and COVID-19 [Internet]. Vol. 177, Antiviral Research. Elsevier B.V.; 2020 [cited 2020 Sep 7]. Available from: https://pubmed.ncbi.nlm.nih.gov/32147496/
10. Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care [Internet]. 2020 Jun 1 [cited 2020 Sep 7];57:279–83. Available from: https://pubmed.ncbi.nlm.nih.gov/32173110/
11. Howes RE, Battle KE, Satyagraha AW, Baird JK, Hay SI. G6PD Deficiency. Global Distribution, Genetic Variants and Primaquine Therapy. In: Advances in Parasitology [Internet]. Academic Press; 2013 [cited 2020 Sep 7]. p. 133–201. Available from: https://pubmed.ncbi.nlm.nih.gov/23384623/
12. Sirdah M, Reading NS, Perkins SL, Shubair M, Aboud L, Prchal JT. Hemolysis and Mediterranean G6PD mutation (c.563 C>T) and c.1311 C>T polymorphism among Palestinians at Gaza Strip. Blood Cells, Mol Dis [Internet]. 2012 Apr 15 [cited 2020 Sep 7];48(4):203–8. Available from: https://pubmed.ncbi.nlm.nih.gov/22364808/
13. SSnpedia.com. 2020. Rs5030868 - Snpedia. [online] Available at:
14. Menounos P, Zervas C, Garinis G, Doukas C, Kolokithopoulos D, Tegos C, et al. Molecular heterogeneity of the glucose-6-phosphate dehydrogenase deficiency in the Hellenic population. Hum Hered [Internet]. 2000 [cited 2020 Sep 7];50(4):237–41. Available from: https://pubmed.ncbi.nlm.nih.gov/10782016/
15. Belfield KD, Tichy EM. Review and drug therapy implications of glucose-6-phosphate dehydrogenase deficiency. Am J Heal Pharm [Internet]. 2018 Feb 1 [cited 2020 Sep 7];75(3):97–104. Available from: https://academic.oup.com/ajhp/article/75/3/97/5102042
16. ph PharmGKB. 2020. Pharmgkb. [online] Available at:
17. Khan M, Paul S, Farooq S, Oo TH, Ramshesh P, Jain N. Rasburicase-Induced Methemoglobinemia in a Patient with Glucose-6- Phosphate Dehydrogenase Deficiency. Curr Drug Saf [Internet]. 2017 May 5 [cited 2020 Sep 7];12(1):13–8. Available from: https://pubmed.ncbi.nlm.nih.gov/28078984
18. Luzzatto L, Nannelli C, Notaro R. Glucose-6-Phosphate Dehydrogenase Deficiency [Internet]. Vol. 30, Hematology/Oncology Clinics of North America. W.B. Saunders; 2016 [cited 2020 Sep 7]. p. 373–93. Available from: https://pubmed.ncbi.nlm.nih.gov/27040960/
19. Ensembl.org. 2020. Rs5030868 (SNP) - Explore This Variant - Homo_Sapiens - Ensembl Genome Browser 101. [online] Available at:
20. Glucose-6 phosphate dehydrogenase mutations and haplotypes in various ethnic groups - PubMed [Internet]. [cited 2020 Sep 7]. Available from: https://pubmed.ncbi.nlm.nih.gov/7803800/
21. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies [Internet]. Vol. 14, BioScience Trends. International Advancement Center for Medicine and Health Research Co., Ltd.; 2020 [cited 2020 Sep 7]. Available from: https://pubmed.ncbi.nlm.nih.gov/32074550/
22. Zhang L, Guo H. Biomarkers of COVID-19 and technologies to combat SARS-CoV-2. Adv Biomark Sci Technol [Internet]. 2020 Aug [cited 2020 Sep 6];2:1. Available from: /pmc/articles/PMC7435336/?report=abstract
23. Macleod JA, Nemeth AC, Dicke WC, Wang D, Manalili Wheeler S, Hannis JC, et al. Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection. Lab Chip [Internet]. 2016 [cited 2020 Sep 18];16(13):2513–20. Available from: https://pubmed.ncbi.nlm.nih.gov/27280174/
24. Wang H, Zhang X, Xu X, Zhang Q, Wang H, Li D, et al. A portable microfluidic platform for rapid molecular diagnostic testing of patients with myeloproliferative neoplasms. Sci Rep [Internet]. 2017 Dec 1 [cited 2020 Sep 18];7(1). Available from: https://pubmed.ncbi.nlm.nih.gov/28819248/
25. Kambouris ME, Siamoglou S, Kordou Z, Milioni A, Vassilakis S, Goudoudaki S, et al. Point-of-need molecular processing of biosamples using portable instrumentation to reduce turnaround time. Biosaf Heal. 2020 Jun 12.
26. Georgios Psarias, Evanthia Iliopoulou, Ioannis Liopetas, Anna Tsironi, Dimitrios Spanos, Athina Tsikrika et al. Development of rapid pharmacogenomic testing assay in a Mobile Molecular Biology Laboratory (2MoBiL). Omi A J Integr Biol. Unpublished data.
27. Dharavath B, Yadav N, Desai S, Sunder R, Mishra R, Ketkar M, et al. A one-step, one-tube real-time RT-PCR based assay with an automated analysis for detection of SARS-CoV-2. Heliyon [Internet]. 2020 Jul 1 [cited 2020 Sep 6];6(7). Available from: https://pubmed.ncbi.nlm.nih.gov/32665985/
28. Chan JFW, Yip CCY, To KKW, Tang THC, Wong SCY, Leung KH, et al. Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-PCR assay validated in vitro and with clinical specimens [Internet]. Vol. 58, Journal of Clinical Microbiology. American Society for Microbiology; 2020 [cited 2020 Sep 6]. Available from: https://pubmed.ncbi.nlm.nih.gov/32132196/
29. Yuan X, Yang C, He Q, Chen J, Yu D, Li J, et al. Current and Perspective Diagnostic Techniques for COVID-19. ACS Infect Dis [Internet]. 2020 Aug 14 [cited 2020 Sep 6];6(8):1998–2016. Available from: /pmc/articles/PMC7409380/?report=abstract
30. Fedorinov DS, Mirzaev KB, Ivashchenko D V., Temirbulatov II, Sychev DA, Maksimova NR, et al. Pharmacogenetic testing by polymorphic markers 681G>A and 636G>A CYP2C19 gene in patients with acute coronary syndrome and gastric ulcer in the Republic of Sakha (Yakutia). Drug Metab Pers Ther [Internet]. 2018 Jun 27 [cited 2020 Sep 6];33(2):91–8. Available from: https://pubmed.ncbi.nlm.nih.gov/29738309/
31. Motawi TK, Shaker OG, El-Maraghy SA, Senousy MA. Serum interferon-related microRNAs as biomarkers to predict the response to interferon therapy in chronic hepatitis C genotype. PLoS One [Internet]. 2015 Mar 19 [cited 2020 Sep 6];10(3). Available from: https://pubmed.ncbi.nlm.nih.gov/25790297/
32. Pisanu C, Congiu D, Costa M, Chillotti C, Ardau R, Severino G, et al. Convergent analysis of genome-wide genotyping and transcriptomic data suggests association of zinc finger genes with lithium response in bipolar disorder. Am J Med Genet Part B Neuropsychiatr Genet [Internet]. 2018 Oct 1 [cited 2020 Sep 6];177(7):658–64. Available from: https://pubmed.ncbi.nlm.nih.gov/30318722/
33. Soloviov OO, Pampukha VM, Livshits LA. Development of ARMS PCR tests for detection of common CFTR gene mutations.
Published
2020-11-19
Section
Πρωτότυπα ερευνητικά άρθρα
