Five genetic polymorphisms of cytochrome P450 enzymes in the Czech non-Roma and Czech Roma population samples
-
Lucie Dlouhá
,
Věra Adámková
Abstract
Objectives
Cytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin.
Methods
Roma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay.
Results
We found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics.
Conclusions
There were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.
Research funding: The study was supported by the project number LD14114, implemented under financial support of the Ministry of Education, Youth and Sports within COST (Cooperation on Scientific and Technical Research), named “Obesity and overweight in Romany minority in the Region of South Bohemia” and by the project (Ministry of Health, Czech Republic) for the development of research organization 00023001 (IKEM, Prague, Czech Republic) – Institutional support.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The study protocol was approved by institutional ethics committee, and conducted according to the Good Clinical Practice guidelines and in agreement with the Helsinki Declaration of 1975.
References
1. Kalaydjieva, L, Gresham, D, Calafell, F. Genetic studies of the Roma (Gypsies): a review. BMC Med Genet 2001;2:2–5. https://doi.org/10.1186/1471-2350-2-5.Search in Google Scholar PubMed PubMed Central
2. Szalai, R, Hadzsiev, K, Melegh, B. Cytochrome P450 drug metabolizing enzymes in Roma population samples: systematic review of the literature. Curr Med Chem 2016;23:3632–52. https://doi.org/10.2174/0929867323666160809092455.Search in Google Scholar PubMed
3. Parry, G, Van Cleemput, P, Peters, J, Walters, S, Thomas, K, Cooper, C. Health status of Gypsies and Travellers in England. J Epidemiol Community Health 2007;61:198–204. https://doi.org/10.1136/jech.2006.045997.Search in Google Scholar PubMed PubMed Central
4. Paulik, E, Nagymajtenyi, L, Easterling, D, Rogers, T. Smoking behaviour and attitudes of Hungarian Roma and non-Roma population towards tobacco control policies. Int J Public Health 2011;56:485–91. https://doi.org/10.1007/s00038-011-0252-x.Search in Google Scholar PubMed PubMed Central
5. Milanov, I, Kmetski, TS, Lyons, KE, Koller, WC. Prevalence of Parkinson’s disease in Bulgarian Gypsies. Neuroepidemiology 2000;19:206–9. https://doi.org/10.1159/000026257.Search in Google Scholar PubMed
6. Kalaydjieva, L, Perez-Lezaun, A, Angelicheva, D, Onengut, S, Dye, D, Bosshard, NU, et al. A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). Am J Hum Genet 1999;65:1299–307. https://doi.org/10.1086/302611.Search in Google Scholar PubMed PubMed Central
7. Forrai, G, Tauszik, T, Tauszik, N, Moh, T, Tunyog, M, Holics, C, et al. A high incidence of PKD in a large geographic area of south-western Hungary: a medical genetic study. Prog Clin Biol Res 1989;305:89–94.Search in Google Scholar
8. Hubacek, JA, Sedova, L, Olisarova, V, Adamková, V, Adamek, V, Tothova, V. Distribution of ADH1B genotypes predisposed to enhanced alcohol consumption in the Czech Roma/Gypsy population. Cent Eur J Public Health 2018;26:284–8. https://doi.org/10.21101/cejph.a5090.Search in Google Scholar PubMed
9. Weber, A, Szalai, R, Sipeky, C, Magyari, L, Melegh, M, Jaromi, L, et al. Increased prevalence of functional minor allele variants of drug metabolizing CYP2B6 and CYP2D6 genes in Roma population samples. Pharmacol Rep 2015;67:460–4. https://doi.org/10.1016/j.pharep.2014.11.006.Search in Google Scholar PubMed
10. Parekh, N, Rose, T. Health inequalities of the Roma in Europe: a literature review. Cent Eur J Public Health 2011;19:139–42.10.21101/cejph.a3661Search in Google Scholar PubMed
11. Hajioff, S, McKee, M. The health of the Roma people: a review of the published literature. J Epidemiol Community Health 2000;54:864–9. https://doi.org/10.1136/jech.54.11.864.Search in Google Scholar PubMed PubMed Central
12. Croom, E. Metabolism of xenobiotics of human environments. Prog Mol Biol Transl Sci 2012;112:31–88. https://doi.org/10.1016/B978-0-12-415813-9.00003-9.Search in Google Scholar PubMed
13. The Human Cytochrome P450 Allele Nomenclature Database. Available from: www.cypalleles.ki.se [Accessed: 12 Dec 2019].Search in Google Scholar
14. Bozina, N, Bradamante, V, Lovrić, M. Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol 2009;60:217–42. https://doi.org/10.2478/10004-1254-60-2009-1885.Search in Google Scholar PubMed
15. Aklillu, E, Carrillo, JA, Makonnen, E, Hellman, K, Pitarque, M, Bertilsson, L, et al. Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1. Mol Pharmacol 2003;64:659–69. https://doi.org/10.1124/mol.64.3.659.Search in Google Scholar PubMed
16. Sachse, C, Brockmöller, J, Bauer, S, Roots, I. Functional significance of a C→A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 1999;47:445–9. https://doi.org/10.1046/j.1365-2125.1999.00898.x.Search in Google Scholar PubMed PubMed Central
17. Tian, Z, Li, YL, Zhao, L, Zhang, CL. Role of CYP1A21F polymorphism in cancer risk: evidence from a metaanalysis of 46 case-control studies. Gene 2013;524:168–74. https://doi.org/10.1016/j.gene.2013.04.038.Search in Google Scholar PubMed
18. Hubacek, JA, Pankova, A, Stepankova, L, Zvolska, K, Adamkova, V, Lanska, V, et al. SNPs within CHRNA5-A3-B4 and CYP2A6/B6 are associated with smoking dependence but not with tobacco dependence treatment outcomes in the Czech population. Gene 2017;606:35–8. https://doi.org/10.1016/j.gene.2017.01.005.Search in Google Scholar PubMed
19. López-Flores, LA, Pérez-Rubio, G, Ramírez-Venegas, A, Ambrocio-Ortiz, E, Sansores, RH, Falfán-Valencia, R. Data on polymorphisms in CYP2A6 associated to risk and predispose to smoking related variables. Data Brief 2017;15:86–91. https://doi.org/10.1016/j.dib.2017.09.013.Search in Google Scholar PubMed PubMed Central
20. Zanger, UM, Klein, K, Saussele, T, Blievernicht, J, Hofmann, MH, et al. Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics 2007;8:743–59. https://doi.org/10.2217/14622416.8.7.743.Search in Google Scholar PubMed
21. Cascorbi, I. Pharmacogenetics of cytochrome P4502D6: genetic background and clinical implication. Eur J Clin Investig 2003;33:17–22. https://doi.org/10.1046/j.1365-2362.33.s2.3.x.Search in Google Scholar PubMed
22. Slanar, O, Drazdakova, M, Babiarova, K, Pechandova, K, Buzkova, H, Perlik, F, et al. Genotyping of CYP2D6 and CYP2C19. Cas Lek Cesk 2007;146:708–11. [Article in Czech].Search in Google Scholar
23. Setia, MS. Methodology series module 5: sampling strategies. Indian J Dermatol 2016;61:505–9. https://doi.org/10.4103/0019-5154.190118.Search in Google Scholar PubMed PubMed Central
24. Adamkova, V, Hubacek, JA, Novakova, D, Dolak, F, Adamek, V, Lanska, V, et al. Genetic and biochemical characteristics in the Roma minority in the South Bohemia Region. Neuro Endocrinol Lett 2015;36(suppl 2):29–34.Search in Google Scholar
25. Tothova, V, Bartlova, S, Sedova, L, Olisarova, V, Prokesova, R, Adamkova, V, et al. The importance of self-management in the prevention and treatment of excessive weight and obesity. Neuro Endocrinol Lett 2015;36(suppl 2):5–10.Search in Google Scholar
26. Hughes, AO, Fenton, S, Hine, CE, Pilgrim, S, Tibbs, N. Strategies for sampling black and ethnic minority populations. J Public Health Med 1995;17:187–92.10.1093/oxfordjournals.pubmed.a043091Search in Google Scholar PubMed
27. Court, MH. 2005-2008. Court-laboratory Hardy-Weinberg calculator. Available from: http://www.tufts.edu/∼mcourt01/Documents/Court%20lab%20-%20HW%20calculator.xls [Accessed: Dec 2019].Search in Google Scholar
28. Kirkman, TW. 1996. Available from: http://www.physics.csbsju.edu/cgi-bin/stats/contingency_form.sh?nrow=2&ncolumn=3 [Accessed Dec 2019].Search in Google Scholar
29. Nair, S, LLerena, A. New perspectives in personalised medicine for ethnicity in cancer: population pharmacogenomics and pharmacometrics. Drug Metab Pers Ther 2018;33:61–4. https://doi.org/10.1515/dmpt-2018-0008.Search in Google Scholar PubMed
30. Rodríguez Vicente, AE, Herrero Cervera, MJ, Bernal, ML, Rojas, L, Peiró, AM. Personalized medicine into health national services: barriers and potentialities. Drug Metab Pers Ther 2018;33:159–63. https://doi.org/10.1515/dmpt-2018-0017.Search in Google Scholar PubMed
31. Lewis, JP, Palmer, ND, Hicks, PJ, Sale, MM, Langefeld, CD, Freedman, BI, et al. Association analysis in african americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies. Diabetes 2008;57:2220–5. https://doi.org/10.2337/db07-1319.Search in Google Scholar PubMed PubMed Central
32. Hubacek, JA. Apolipoprotein L1 – etnically specific determinant of renal and heart failure. AtheroRev 2019;4:159–61. [Article in Czech].Search in Google Scholar
33. Hubacek, JA, Adamkova, V, Šedova, L, Olisarová, V, Adamek, V, Tothova, V. Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations. Genet Mol Biol 2017;40:450–2. https://doi.org/10.1590/1678-4685-GMB-2016-0071.Search in Google Scholar PubMed PubMed Central
34. Hofmann, MH, Blievernicht, JK, Klein, K, Saussele, T, Schaeffeler, E, Schwab, M, et al. Aberrant splicing caused by single nucleotide polymorphism c.516G>T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CYP2B6 in liver. J Pharmacol Exp Ther 2008;325:284–92. https://doi.org/10.1124/jpet.107.133306.Search in Google Scholar PubMed
35. PubMed database. Available from: https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?do_not_redirect&rs=rs4105144 [Accessed Dec 2019].Search in Google Scholar
36. Úřad Vlády, ČR. National report 2009 about Roma population. Available from: https://www.vlada.cz/assets/ppov/zalezitosti-romske-komunity/dokumenty/Sastipen.pdf [Accessed Dec 2019].Search in Google Scholar
37. Mravcik, V, Chomynova, P, Grohmannova, K, Janikova, B, Cernikova, T, Rous, Z, et al. Annual Report on Drug Situation 2017 - Czech Republic. Úřad vlády České republiky 2017. Available from: https://www.drogy-info.cz/data/obj_files/32962/837/VZdrogy2017_web181207.pdf [Accessed Dec 2019].Search in Google Scholar
38. Paradkar, MU, Shah, SA, Dherai, AJ, Shetty, D, Ashavaid, TF. Distribution of CYP2D6 genotypes in the Indian population - preliminary report. Drug Metab Pers Ther 2018;33:141–51. https://doi.org/10.1515/dmpt-2018-0011.Search in Google Scholar PubMed
39. Teh, LK, Mohamed, NI, Salleh, MZ, Rohaizak, M, Shahrun, NS, Saladina, JJ, et al. The risk of recurrence in breast cancer patients treated with tamoxifen: polymorphisms of CYP2D6 and ABCB1. AAPS J 2012;14:52–9. https://doi.org/10.1208/s12248-011-9313-6.Search in Google Scholar PubMed PubMed Central
40. Szalai, R, Magyari, L, Matyas, P, Duga, B, Banfai, Z, Szabo, A, et al. Genetic polymorphisms in promoter and intronic regions of CYP1A2 gene in Roma and Hungarian population samples. Environ Toxicol Pharmacol 2014;38:814–20. https://doi.org/10.1016/j.etap.2014.09.012.Search in Google Scholar PubMed
41. Di, YM, Chow, VD, Yang, LP, Zhou, SF. Structure, function, regulation and polymorphism of human cytochrome P450 2A6. Curr Drug Metab. 2009; 10:754–80. https://doi.org/10.2174/138920009789895507.Search in Google Scholar PubMed
42. Martínez-Cruz, B, Mendizabal, I, Harmant, C, de Pablo, R, Ioana, M, Angelicheva, D, et al. Origins, admixture and founder lineages in European Roma. Eur J Hum Genet 2016;24:937–43. https://doi.org/10.1038/ejhg.2015.201.Search in Google Scholar PubMed PubMed Central
43. Gusmão, A, Valente, C, Gomes, V, Alves, C, Amorim, A, Prata, MJ, et al. A genetic historical sketch of European Gypsies: The perspective from autosomal markers. Am J Phys Anthropol 2010;141:507–14. https://doi.org/10.1002/ajpa.21166.Search in Google Scholar PubMed
44. Regueiro, M, Stanojevic, A, Chennakrishnaiah, S, Rivera, L, Varljen, T, Alempijevic, D, et al. Divergent patrilineal signals in three Roma populations. Am J Phys Anthropol 2011;144:80–91. https://doi.org/10.1002/ajpa.21372.Search in Google Scholar PubMed
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Original Articles
- Five genetic polymorphisms of cytochrome P450 enzymes in the Czech non-Roma and Czech Roma population samples
- Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms
- The particulars of certain drugs’ effect on the endogenous coenzyme Q10 plasma level in patients with cardiovascular diseases
- Evaluation of the suitability of 19 pharmacogenomics biomarkers for individualized metformin therapy for type 2 diabetes patients
- Self-estimation of phenylketonuria patients on therapeutic diet. Psychological support
- Double-blind trial of solid lipid Boswellia serrata particles (SLBSP) vs. standardized Boswellia serrata gum extract (BSE) for osteoarthritis of knee
- Case Report
- Meropenem for management of valproic acid overdose: a case report
Articles in the same Issue
- Original Articles
- Five genetic polymorphisms of cytochrome P450 enzymes in the Czech non-Roma and Czech Roma population samples
- Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms
- The particulars of certain drugs’ effect on the endogenous coenzyme Q10 plasma level in patients with cardiovascular diseases
- Evaluation of the suitability of 19 pharmacogenomics biomarkers for individualized metformin therapy for type 2 diabetes patients
- Self-estimation of phenylketonuria patients on therapeutic diet. Psychological support
- Double-blind trial of solid lipid Boswellia serrata particles (SLBSP) vs. standardized Boswellia serrata gum extract (BSE) for osteoarthritis of knee
- Case Report
- Meropenem for management of valproic acid overdose: a case report
