UKRAINS'KYI VISNYK PSYKHONEVROLOHII

The Scientific and Practical Journal of Medicine
ISSN 2079-0325(p)
DOI 10.36927/2079-0325
Home » Archive of numbers » 2018 » Volume 26, issue 3 (96) » Pharmacogenetic testing as a basis for the selection of antiepileptic drugs in the treatment of pharmacoresistant epilepsy in children

Pharmacogenetic testing as a basis for the selection of antiepileptic drugs in the treatment of pharmacoresistant epilepsy in children

Authors

Type of Article

  • Scientific Article

In the Section

  • PROBLEMATIC ARTICLES

Key words

Index UDK:
  • 616.853-056.7: 615.213-08: 575.113.2

Abstract

We analyzed the results of an examination of 68 patients (children and adolescents), 42 (62.69 %) boys and 26 (37.31 %) girls, aged 5 months to 18 years, the average age was 9.6 ± 5.65 years. Children suffer from severe, refractory to the treatment forms of epilepsy. Duration of the disease from 1 month to 16 years. All children were given genetic research using the allelic method CYP2C9*1,*2,*3 of a specifi c polymerase chain reaction. In the study group dominated homozygous carriers by the allele CYP2C9*1 — 76.47 %. This genotype is quite common in many populations and is typical for fast meta bolism. The carrier of CYP2C9*2 and CYP2C9*3 alleles, which is functionally linked with biotransformation of drugs, slowing down their metabolism and occurrence of side effects, was found in 22.53 % of patients.

Pages

  • 5-9

Year / Issue

Download PDF

References

  1. Genetic passport - the basis of individual and predictive medicine / ed. by V. S. Baranov. S. Baranov. SPb.: Izd-vo N-L, 2009. 528 с.
  2. Gerasimova K. V., Sychev D. A. Clinical pharmacogenetics: a historical sketch // Medical technologies. Evaluation and choice. 2012. № 3. С. 87-94.
  3. Anderson G. Pharmacokinetic, pharmacodynamic, and pharmacogenetic targeted therapy of  antiepileptic drugs  // Ther. Drug Monit. 2008. 30; 173—180.
  4. Seredenin S. B. Lectures on pharmacogenetics. Moscow: Medical Information Agency, 2004. 303 с.
  5. Luscher W., Klotz U., Zimprich E., Schmidt D. The clinical impact of pharmacogenetics on the treatment of epilepsy // Epilepsia. 2009 Jan; 50 (1): 1—23.
  6. Kukes V.G., Grachev S. V. V., Sychev D. A., Ramenskaya G. V. Drug metabolism // Scientific bases of personalized medicine : a guide for doctors. V. Metabolism of drugs // Scientific bases of personalized medicine : a guide for doctors. Moscow: GEOTARMedia, 2008. 304 с.
  7. Glauser T. Biomarkers for antiepileptic drug response  // Biomark Med. 2011 Oct; 5 (5): 635—41.
  8. Franco V., Perucca E. CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects // Expert Opin Drug Metab Toxicol. 2015; 11 (8): 1269—79.
  9. Depondt C. Epilepsy pharmacogenetics: science or fi ction? // Med Sci (Paris). 2013; 29 (2): 189—93. doi: https://doi.org/1051/medsci/2013292017.
  10. Glauser T. A. Biomarkers for antiepileptic drug response // Biomark Med. 2011 Oct; 5 (5): 635—41.
  11. Pharmacogenetics and antiepileptic drug metabolism: implication of genetic variants in cytochromes P450  / SaldañaCruz A. M., Sánchez-Corona J., Márquez de Santiago D. A. [et al.] // Rev Neurol. 2013 May 1; 56 (9): 471—9.
  12. Genetic polymorphism analysis of the drug-metabolizing enzyme CYP2C9 in a Chinese Tibetan population / Jin T., Geng T., He N. [et al.] // Gene. 2015; 567: 196—200.
  13. Genetic polymorphisms of VKORC1, CYP2C9, CYP4F2 in Bai, Tibetan Chinese / W.   Zeng, Q.  S.  Zheng, M. Huang [et  al.]  // Pharmazie. 2012; 67: 69—73.
  14. CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database / D-P. Dai, R-A.  Xu, L-M. Hu [et al.] // Pharmacogenomics J. 2014; 14: 85—92.
  15. Allele and genotype frequencies of CYP2C9 in a Korean population / Bae J.-W., Kim H.-K., Kim J.-H. [et al.] // Br J Clin Pharmacol. 2005; 60: 418—422. doi: https://doi.org/1111/j.1365-2125.2005.02448.x.
  16. Frequency of cytochrome P450 2C9 mutant alleles in a Korean population / Yoon Y. , Shon J.  H., Kim  M.  K. [et  al.]  // Br  J  Clin Pharmacol. 2001; 51: 277—280.
  17. Nasu K., Kubota T., Ishizaki T. Genetic analysis of CYP2C9 polymorphism in a  Japanese population  // Pharmacogenetics. 1997; 7: 405—409.
  18. Zuo J., Xia D., Jia L., Guo T. Genetic polymorphisms of drugmetabolizing phase I enzymes CYP3A4, CYP2C9, CYP2C19 and CYP2D6 in Han, Uighur, Hui and Mongolian Chinese populations // Pharmazie. 2012; 67: 639—644.
  19. Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Mongolian population in China / Yang Z. F., Cui H. W., Hasi T. [et al.] // Genet Mol Res. 2010; 9: 1844—1851.
  20. Genetic polymorphism of CYP2C9 in a  Vietnamese Kinh population  / Lee    S., Kim  K.  M., Thi-Le  H. [et  al.]  // Ther Drug Monit. 2005; 27: 208—210.
  21. CYP2C9 polymorphism: prevalence in healthy and warfarintreated Malay and Chinese in Malaysia / Ngow H. A., Wan Khairina W. M., Teh L. K. [et al.] // Singapore Med J. 2009; 50: 490—493.
  22. Allele and genotype frequency of CYP2C9 in Tamilnadu population / Adithan C., Gerard N., Vasu S. [et  ]  // Eur  J  Clin Pharmacol. 2003; 59: 707—709.
  23. Alzahrani M., Ragia G., Hanieh H., Manolopoulos V.  G. Genotyping of CYP2C9 and VKORC1 in the Arabic population of AlAhsa, Saudi Arabia  // BioMed Res  Int. 2013; Vol.  2013, Article ID 315980, 6 p. URL : http://dx.doi.org/10.1155/2013/315980
  24. Mirghani A., Chowdhary G., Elghazali G. Distribution of the major cytochrome P450 (CYP) 2C9 genetic variants in a Saudi population // Basic Clin Pharmacol Toxicol. 2011; 109: 111—114.
  25. Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population  / Hamdy    I., Hiratsuka  M., Narahara K. [et  al.]  // Br  J  Clin Pharmacol. 2002; 53: 596—603.
  26. Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population  / Yousef A.  , Bulatova N. R., Newman W. [et al.] // Mol Biol Rep. 2012; 39: 9423—9433.
  27. Pharmacogenetics of coumarin dosing: prevalence of CYP2C9 and VKORC1 polymorphisms in the Lebanese population / DjaffarJureidini , Chamseddine N., Keleshian S. [et al.]  // Genet Test Mol Biomarkers. 2011; 15: 827—830.
  28. Frequency of CYP2C9 genotypes among Omani patients receiving warfarin and its correlation with warfarin dose / Tanira M. O., Al-Mukhaini M. K., Al-Hinai A. T. [et al.] // Community Genet. 2007; 10: 32—37.
  29. Ge n e t i c p o l y m o r p h i s m o f c y t o c h ro m e P 4 5 0 2 C 9 in a  Caucasian and a  black African population  / Scordo M.  G., Aklillu E., Yasar U. [et al.] // Br J Clin Pharmacol. 2001; 52: 447—450.
  30. Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups / Scott S. A., Khasawneh R., Peter I. [et al.] // Pharmacogenomics. 2010; 11: 781—791.
  31. Influence of CYP2C9 Genotype on warfarin dose among African American and European Americans / Limdi N., Goldstein J., Blaisdell J. [et al.] // Per Med. 2007; 4: 157—169.
  32. Kudzi W., Dodoo A. N., Mills J. J. Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population. BMC Med Genet. 2009; 10: 124.
  33. Zand N., Tajik N., Moghaddam A. , Milanian I. Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in  a  healthy Iranian population  // Clin Exp  Pharmacol Physiol. 2007;
  34. 34: 102—105. 34. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin / Aynacioglu A. S., Brockmoller , Bauer S. [et al.]  // Br  J  Clin Pharmacol. 1999; 48: 409—415.
  35. CYP2C9 genotypes and the quality of anticoagulation control with warfarin therapy among Brazilian patients / Lima V., Ribeiro  G.  S., Mesquita E. T. [et  al.]  // Eur  J  Clin Pharmacol. 2008; 64: 9—15.
  36. Lower frequency of CYP2C9*2 in Mexican-Americans compared to Spaniards / LLerena A., Dorado P., O’Kirwan F. [et  ]  // Pharmacogenomics J. 2004; 4: 403—406.  =  Lower frequency of CYP2C9*2 in Mexican-Americans compared to Spaniards.
  37. Losartan hydroxylation phenotype in an Ecuadorian population: influence of CYP2C9 genetic polymorphism, habits and gender / Dorado , Beltrán L. J., Machín E. [et  al.]  // Pharmacogenomics. 2012; 13: 1711—1717.
  38. Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a  Swedish population  / Yasar  , Eliasson  E., Dahl  M.  L. [et  al.]  // Biochem Biophys Res  Commun. 1999; 254: 628—631.
  39. Microarray-based detection of CYP1A1, CYP2C9, CYP2C19, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, NAT2, HLA-DQA1, and AB0 allele frequencies in native Russians / Gra O., Mityaeva O., Berdichevets I. [et ] // Genet Test Mol  Biomarkers. 2010; 14: 329—342.
  40. Genetic analysis of the human cytochrome P450 CYP2C9 locus / Stubbins M. J., Harries L. W., Smith G. [et al.] // Pharmacogenetics. 1996; 6: 429—439.
  41. Pharmacogenetically relevant polymorphisms in Portugal / Oliveira E., Marsh S., van Booven D. J. [et al.] // Pharmacogenomics. 2007; 8: 703—712.
  42. Prevalence of CYP2C9 polymorphisms in the south of  Europe  / Sanchez-Diz  , Estany-Gestal A., Aguirre C. [et  al.]  // Pharmaco geno mics J. 2009; 9: 306—310.
  43. Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French populations / Yang J. Q., Morin S., Verstuyft C. [et al.] // Fundam Clin Pharmacol. 2003; 17: 373—376.
  44. Genetic polymorphism of CYP2C9 and CYP2C19 in a Bolivian population: an investigative and comparative study / BravoVillalta    V., Yamamoto K., Nakamura K. [et  al.]  // Eur  J  Clin Pharmacol. 2005; 61: 179—184.
  45. Interethnic differences in the relevance of CYP2C9 genotype and environmental factors for diclofenac metabolism in Hispanics from Cuba and Spain / Llerena A., Alvarez M., Dorado P. [et al.] // Pharmaco genomics J. 2014; 14: 229—234.
  46. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism / Sullivan-Klose T. H., Ghanayem B. I., Bell D. A. [et al.] // Pharmacogenetics. 1996; 6: 341—349.
  47. Genetic polymorphisms of cytochromes P450: CYP2C9, CYP2C19, and CYP2D6 in Croatian population / Bozina N., Granic P., Lalic Z. [et al.] // Croat Med J. 2003; 44: 425—428.
  48. Burian M., Grosch S., Tegeder I., Geisslinger G. Validation of a new fluorogenic real-time PCR assay for detection of CYP2C9 allelic variants and CYP2C9 allelic distribution in a German population // Br J Clin Pharmacol. 2002; 54: 518—521.
  49. Genetic polymorphisms of drug-metabolizing enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 in the Greek population / Arvanitidis K., Ragia G., Iordanidou M. [et ]  // Fundam Clin Pharmacol. 2007; 21: 419—426.
  50. Antonenko PB, Kresyun VI Polymorphism of cytochrome P450 2C9 genotype in the Odesa region // Actual problems of modern medicine. 2011. № 11(4). С. 51-55.
  51. Levkovych N.M., Horovenko N.G. Frequency of distribution of allelic variants *2 and *3 of the SUR2C9 gene in the population of Ukraine // Odesa Medical Journal. 2013. № 2 (136). С. 23-28.
  52. Guzeva O.. V. Optimization of diagnosis and justification of personalized therapy of epilepsy in children : author's thesis for the degree of Doctor of Medical Sciences : specialty 01.11 "Nervous Diseases". St. Petersburg, 2014, P. 34.
  53. The Effect of Polymorphisms of Cytochrom P450 CYP2C9, CYP2C19 and CYP2D6 on Drug-Resistant Epilepsy in Turkish Children / Seven M., Batar B., Unal S. [et al.] // Molecular Diagnosis&Therapy. 2014; Vol. 18: 229—236.
  54. Frequencies of CYP2C9 polymorphisms in Nord Indian population and their association with drug levels in  children on  phenytoin monotherapy  / Сhaudhary N., Kabra M., Gulati  [et al.] // BMC Pediatr. 2016.

Journal’s Indexing:

UKRAINS'KYI VISNYK PSYKHONEVROLOHII

The Scientific and Practical Journal of Medicine

ДУ «ІНПН імені
П.В. ВОЛОШИНА
НАМН УКРАЇНИ»