The Current Status of Genes and Genetic Testing in Emergency Medicine: A Narrative Review
Abstract
Context: An emergency is any medical problem that could cause death or permanent injury if not treated quickly. In some occasions, the kind of urgent intervention depends on patient’s exact genetic background. Unfortunately, the importance of genes in medical emergencies has been forgotten in recent decades.
Evidence acquisition: In order to find relevant articles, we searched two databases of Pubmed and Embase. The exact words of “genes”, “genetics”, “epigenetics”, “DNA”, and “emergency” were used alone and in combination. All studies like randomized clinical trials (RCT), case/controls, case series, case reports, and review articles were studied to find the related data. No time limitation was considered for the studies.
Results: Several aspects of genetic testing are newly considered in emergency departments including cell-free DNA (cfDNA) for disease diagnosis, pharmacogenetics for decreasing the adverse drug effects, and personalized medicine for exact emergency interventions in diseases like Vascular Ehlers-Danlos syndrome (vEDS). Data from genetic testing and genome wide association studies have yielded promising results to make medical emergency interventions more beneficial in the near future.
Conclusion: Taking everything into consideration, several advanced genetic and epigenetic alteration technologies can change emergency medicine for the better. Personalized genetic data of patients can turn emergency medicine to personalized medicine.
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13. Jain K. Personalized medicine. Curr Opin Mol Ther. 2002;4(6):548-58.
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15. Burke W. Genetic testing. N Engl J Med. 2002;347(23):1867-75.
16. Wang T-L, Maierhofer C, Speicher MR, Lengauer C, Vogelstein B, Kinzler KW, et al. Digital karyotyping. Proc Natl Acad Sci U S A. 2002;99(25):16156-61.
17. Norton ME, Kuller JA, Dugoff L. Perinatal Genetics: Elsevier Health Sciences; 2019.
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21. Kenneth Jr M, LeGrand SM. The protein folding problem and tertiary structure prediction: Springer Science & Business Media; 2012.
22. Onuchic JN, Wolynes PG. Theory of protein folding. Curr Opin Struct Biol. 2004;14(1):70-5.
23. Mallamace F, Corsaro C, Mallamace D, Vasi S, Vasi C, Baglioni P, et al. Energy landscape in protein folding and unfolding. Proc Natl Acad Sci U S A. 2016;113(12):3159-63.
24. Loonen AJ, de Jager CP, Tosserams J, Kusters R, Hilbink M, Wever PC, et al. Biomarkers and molecular analysis to improve bloodstream infection diagnostics in an emergency care unit. PloS one. 2014;9(1):e87315.
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28. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138-50.
29. Pepin MG, Murray ML, Byers PH. Vascular Ehlers-Danlos syndrome. GeneReviews®[Internet]: University of Washington, Seattle; 2015.
30. Watanabe A, Kosho T, Wada T, Sakai N, Fujimoto M, Fukushima Y, et al. Genetic aspects of the vascular type of Ehlers-Danlos syndrome (vEDS, EDSIV) in Japan. Circ J. 2007;71(2):261-5.
31. Frank M, Albuisson J, Ranque B, Golmard L, Mazzella J-M, Bal-Theoleyre L, et al. The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers–Danlos syndrome. Eur J Hum Genet. 2015;23(12):1657-64.
32. Kahlert C. Liquid Biopsy: Is There an Advantage to Analyzing Circulating Exosomal DNA Compared to cfDNA or Are They the Same? Cancer Res. 2019;79(10):2462-5.
33. Volik S, Alcaide M, Morin RD, Collins C. Cell-free DNA (cfDNA): clinical significance and utility in cancer shaped by emerging technologies. Mol Cancer Res. 2016;14(10):898-908.
34. Diaz IM, Nocon A, Mehnert DH, Fredebohm J, Diehl F, Holtrup F. Performance of Streck cfDNA blood collection tubes for liquid biopsy testing. PLoS One. 2016;11(11):e0166354.
35. Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ, Makarewicz AJ, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem. 2011;83(22):8604-10.
36. Hayden R, Gu Z, Ingersoll J, Abdul-Ali D, Shi L, Pounds S, et al. Comparison of droplet digital PCR to real-time PCR for quantitative detection of cytomegalovirus. J Clin Microbiol. 2013;51(2):540-6.
37. Quail MA, Kozarewa I, Smith F, Scally A, Stephens PJ, Durbin R, et al. A large genome center's improvements to the Illumina sequencing system. Nat Methods. 2008;5(12):1005-10.
38. Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, et al. Melanomas acquire resistance to B-RAF (V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468(7326):973-7.
39. Jabara CB, Jones CD, Roach J, Anderson JA, Swanstrom R. Accurate sampling and deep sequencing of the HIV-1 protease gene using a Primer ID. Proc Natl Acad Sci U S A. 2011;108(50):20166-71.
40. Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B. Detection and quantification of rare mutations with massively parallel sequencing. Proc Natl Acad Sci U S A. 2011;108(23):9530-5.
41. Srugo I, Klein A, Stein M, Golan-Shany O, Kerem N, Chistyakov I, et al. Validation of a novel assay to distinguish bacterial and viral infections. Pediatrics. 2017;140(4):e20163453.
42. Hoeboer SH, van der Geest PJ, Nieboer D, Groeneveld AJ. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2015;21(5):474-81.
43. Moreira VG, Prieto B, Rodriguez JS, Alvarez FV. Usefulness of cell-free plasma DNA, procalcitonin and C-reactive protein as markers of infection in febrile patients. Ann Clin Biochem. 2010;47(Pt 3):253-8.
44. Rannikko J, Seiskari T, Huttunen R, Tarkiainen I, Jylhävä J, Hurme M, et al. Plasma cell‐free DNA and qSOFA score predict 7‐day mortality in 481 emergency department bacteraemia patients. J Intern Med. 2018;284(4):418-26.
45. Chornenki NLJ, Coke R, Kwong AC, Dwivedi DJ, Xu MK, McDonald E, et al. Comparison of the source and prognostic utility of cfDNA in trauma and sepsis. Intensive Care Med Exp. 2019;7(1):29.
46. Gabe ME, Davies GA, Murphy F, Davies M, Johnstone L, Jordan S. Adverse drug reactions: treatment burdens and nurse‐led medication monitoring. J Nurs Manag. 2011;19(3):377-92.
47. Daly AK. Pharmacogenomics of adverse drug reactions. Genome Med. 2013;5(1):5.
48. Limkakeng AT, Jr., Monte AA, Kabrhel C, Puskarich M, Heitsch L, Tsalik EL, et al. Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine? Acad Emerg Med. 2016;23(10):1097-106.
49. Elliott LS, Henderson JC, Neradilek MB, Moyer NA, Ashcraft KC, Thirumaran RK. Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial. PloS one. 2017;12(2):e0170905.
2. Desierto DA. Necessity and national emergency clauses: sovereignty in modern treaty interpretation. Brill Nijhoff; 2012.
3. Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001;286(18):2270-9.
4. Callegari C, Isella C, Caselli I, Poloni N, Ielmini M. Pharmacogenetic Tests in Reducing Accesses to Emergency Services and Days of Hospitalization in Bipolar Disorder: A 2-Year Mirror Analysis. J Pers Med. 2019;9(2):E22.
5. Schuetz P, Haubitz S, Mueller B. Do sepsis biomarkers in the emergency room allow transition from bundled sepsis care to personalized patient care? Curr Opin Crit Care. 2012;18(4):341-9.
6. Collins FS, McKusick VA. Implications of the Human Genome Project for medical science. JAMA. 2001;285(5):540-4.
7. Rando OJ, Verstrepen KJ. Timescales of genetic and epigenetic inheritance. Cell. 2007;128(4):655-68.
8. Christensen K, Murray JC. What genome-wide association studies can do for medicine. N Engl J Med. 2007;356(11):1094-7.
9. Hood L, Rowen L. The human genome project: big science transforms biology and medicine. Genome Med. 2013;5(9):79.
10. Ikram MK, Xueling S, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, et al. Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. PLoS Genet. 2010;6(10):e1001184.
11. Xu Z, Taylor JA. SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res. 2009;37(Web Server issue):W600-5.
12. Hamburg MA, Collins FS. The path to personalized medicine. N Engl J Med. 2010;363(4):301-4.
13. Jain K. Personalized medicine. Curr Opin Mol Ther. 2002;4(6):548-58.
14. Whirl‐Carrillo M, McDonagh EM, Hebert J, Gong L, Sangkuhl K, Thorn C, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012; 92(4): 414-7.
15. Burke W. Genetic testing. N Engl J Med. 2002;347(23):1867-75.
16. Wang T-L, Maierhofer C, Speicher MR, Lengauer C, Vogelstein B, Kinzler KW, et al. Digital karyotyping. Proc Natl Acad Sci U S A. 2002;99(25):16156-61.
17. Norton ME, Kuller JA, Dugoff L. Perinatal Genetics: Elsevier Health Sciences; 2019.
18. Metzker ML. Sequencing technologies—the next generation. Nat Rev Genet. 2010;11(1):31-46.
19. Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008;26(10):1135-45.
20. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013;369(16):1502-11.
21. Kenneth Jr M, LeGrand SM. The protein folding problem and tertiary structure prediction: Springer Science & Business Media; 2012.
22. Onuchic JN, Wolynes PG. Theory of protein folding. Curr Opin Struct Biol. 2004;14(1):70-5.
23. Mallamace F, Corsaro C, Mallamace D, Vasi S, Vasi C, Baglioni P, et al. Energy landscape in protein folding and unfolding. Proc Natl Acad Sci U S A. 2016;113(12):3159-63.
24. Loonen AJ, de Jager CP, Tosserams J, Kusters R, Hilbink M, Wever PC, et al. Biomarkers and molecular analysis to improve bloodstream infection diagnostics in an emergency care unit. PloS one. 2014;9(1):e87315.
25. Kung C-T, Hsiao S-Y, Tsai T-C, Su C-M, Chang W-N, Huang C-R, et al. Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room. J Transl Med. 2012;10(1):130.
26. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228.
27. Esteban A, Frutos-Vivar F, Ferguson ND, Peñuelas O, Lorente JÁ, Gordo F, et al. Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward. Crit Care Med. 2007;35(5):1284-9.
28. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138-50.
29. Pepin MG, Murray ML, Byers PH. Vascular Ehlers-Danlos syndrome. GeneReviews®[Internet]: University of Washington, Seattle; 2015.
30. Watanabe A, Kosho T, Wada T, Sakai N, Fujimoto M, Fukushima Y, et al. Genetic aspects of the vascular type of Ehlers-Danlos syndrome (vEDS, EDSIV) in Japan. Circ J. 2007;71(2):261-5.
31. Frank M, Albuisson J, Ranque B, Golmard L, Mazzella J-M, Bal-Theoleyre L, et al. The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers–Danlos syndrome. Eur J Hum Genet. 2015;23(12):1657-64.
32. Kahlert C. Liquid Biopsy: Is There an Advantage to Analyzing Circulating Exosomal DNA Compared to cfDNA or Are They the Same? Cancer Res. 2019;79(10):2462-5.
33. Volik S, Alcaide M, Morin RD, Collins C. Cell-free DNA (cfDNA): clinical significance and utility in cancer shaped by emerging technologies. Mol Cancer Res. 2016;14(10):898-908.
34. Diaz IM, Nocon A, Mehnert DH, Fredebohm J, Diehl F, Holtrup F. Performance of Streck cfDNA blood collection tubes for liquid biopsy testing. PLoS One. 2016;11(11):e0166354.
35. Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ, Makarewicz AJ, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem. 2011;83(22):8604-10.
36. Hayden R, Gu Z, Ingersoll J, Abdul-Ali D, Shi L, Pounds S, et al. Comparison of droplet digital PCR to real-time PCR for quantitative detection of cytomegalovirus. J Clin Microbiol. 2013;51(2):540-6.
37. Quail MA, Kozarewa I, Smith F, Scally A, Stephens PJ, Durbin R, et al. A large genome center's improvements to the Illumina sequencing system. Nat Methods. 2008;5(12):1005-10.
38. Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, et al. Melanomas acquire resistance to B-RAF (V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468(7326):973-7.
39. Jabara CB, Jones CD, Roach J, Anderson JA, Swanstrom R. Accurate sampling and deep sequencing of the HIV-1 protease gene using a Primer ID. Proc Natl Acad Sci U S A. 2011;108(50):20166-71.
40. Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B. Detection and quantification of rare mutations with massively parallel sequencing. Proc Natl Acad Sci U S A. 2011;108(23):9530-5.
41. Srugo I, Klein A, Stein M, Golan-Shany O, Kerem N, Chistyakov I, et al. Validation of a novel assay to distinguish bacterial and viral infections. Pediatrics. 2017;140(4):e20163453.
42. Hoeboer SH, van der Geest PJ, Nieboer D, Groeneveld AJ. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2015;21(5):474-81.
43. Moreira VG, Prieto B, Rodriguez JS, Alvarez FV. Usefulness of cell-free plasma DNA, procalcitonin and C-reactive protein as markers of infection in febrile patients. Ann Clin Biochem. 2010;47(Pt 3):253-8.
44. Rannikko J, Seiskari T, Huttunen R, Tarkiainen I, Jylhävä J, Hurme M, et al. Plasma cell‐free DNA and qSOFA score predict 7‐day mortality in 481 emergency department bacteraemia patients. J Intern Med. 2018;284(4):418-26.
45. Chornenki NLJ, Coke R, Kwong AC, Dwivedi DJ, Xu MK, McDonald E, et al. Comparison of the source and prognostic utility of cfDNA in trauma and sepsis. Intensive Care Med Exp. 2019;7(1):29.
46. Gabe ME, Davies GA, Murphy F, Davies M, Johnstone L, Jordan S. Adverse drug reactions: treatment burdens and nurse‐led medication monitoring. J Nurs Manag. 2011;19(3):377-92.
47. Daly AK. Pharmacogenomics of adverse drug reactions. Genome Med. 2013;5(1):5.
48. Limkakeng AT, Jr., Monte AA, Kabrhel C, Puskarich M, Heitsch L, Tsalik EL, et al. Systematic Molecular Phenotyping: A Path Toward Precision Emergency Medicine? Acad Emerg Med. 2016;23(10):1097-106.
49. Elliott LS, Henderson JC, Neradilek MB, Moyer NA, Ashcraft KC, Thirumaran RK. Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial. PloS one. 2017;12(2):e0170905.
| Files | ||
| Issue | Vol 4 No 1 (2020): Winter (February) | |
| Section | Review article | |
| PMCID | PMC6955026 | |
| PMID | 31938779 | |
| Keywords | ||
| Emergency Medicine Pharmacogenetics Precision Medicine | ||
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How to Cite
1.
Aghamir S-M-K, Ebrahimi M, Khatami F. The Current Status of Genes and Genetic Testing in Emergency Medicine: A Narrative Review. Front Emerg Med. 2019;4(1):e10.
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