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A Decade of Pharmacogenetic Studies in Jordan: A Systemic Review

The Pharmacogenomics Journal volume 21, pages 543–550 (2021)Cite this article

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Abstract

The aim of this study was to perform a systematic overview of the pharmacogenetic studies conducted in Jordan. A structured search of Medline was conducted for articles over the last decade (January 2010–July 2020). Studies were classified by design, sample size, drug–gene combination, and the significance of the results. Thirty-two studies met the criteria for review. Most pharmacogenomic studies had a case-only design (n = 23). Only five studies included >500 participants. The total number of genetic variants in all studies was one hundred fifteen, which were found in forty genes, including dynamic (n = 27), and kinetic (n = 9) genes. The most commonly studied drugs were within the hematology and cardiology therapeutic areas and included statins, warfarin, aspirin, and clopidogrel. Most studies (n = 18) reported results with mixed p values [<0.05 and >0.05]. Pharmacogenomic research in Jordan is still in its infancy and is limited mainly to replication attempts. The need for standardization is imperative, especially in developing countries with scarce funding resources.

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Fig. 1: Flowchart demonstrating the methodology for identifying pharmacogenetic studies in the systematic review.
Fig. 2: Gene classifications in pharmacogenetic studies.
Fig. 3: Percentage of pharmacogenetic studies that investigated a single gene versus multiple genes.
Fig. 4: Drug-gene combination in pharmacogenetic studies.

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References

  1. Ramsay M. Precision medicine for Africa: challenges and opportunities. Quest. 2018;14:28–32.

    Google Scholar 

  2. Zhu Y, Swanson KM, Rojas RL, Wang Z, Sauver JLS, Visscher SL, et al. Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases. Genet Med. 2020;22:475–86.

  3. Payne K, Gavan SP, Wright SJ, Thompson AJ. Cost-effectiveness analyses of genetic and genomic diagnostic tests. Nat Rev Genet. 2018;19:235.

    Article  CAS  PubMed  Google Scholar 

  4. Pirmohamed M. Pharmacogenetics and pharmacogenomics. Br J Clin Pharmacol. 2001;52:345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bartfai T. Pharmacogenomics in drug development: societal and technical aspects. Pharmacogenomics J. 2004;4:226–32.

    Article  CAS  PubMed  Google Scholar 

  6. Ross JS, Symmans WF, Pusztai L, Hortobagyi GN. Pharmacogenomics and clinical biomarkers in drug discovery and development. Pathol Patterns Rev. 2005;124 Suppl 1:S29–41.

    Article  CAS  Google Scholar 

  7. Lee JW, Aminkeng F, Bhavsar A, Shaw K, Carleton B, Hayden M, et al. The emerging era of pharmacogenomics: current successes, future potential, and challenges. Clin Genet. 2014;86:21–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. US Food and Drug Administration. FDA authorizes first direct-to-consumer test for detecting genetic variants that may be associated with medication metabolism. 2018.

  9. Pirmohamed M. The applications of pharmacogenetics to prescribing: what is currently practicable? Clin Med. 2009;9:493.

    Article  Google Scholar 

  10. Goldstein DB, Tate SK, Sisodiya SM. Pharmacogenetics goes genomic. Nat Rev Genet. 2003;4:937–47.

    Article  CAS  PubMed  Google Scholar 

  11. Zeng X, Zhang Y, Kwong JS, Zhang C, Li S, Sun F, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta‐analysis, and clinical practice guideline: a systematic review. J Evid Based Med. 2015;8:2–10.

    Article  PubMed  Google Scholar 

  12. Alonso-Coello P, Irfan A, Solà I, Gich I, Delgado-Noguera M, Rigau D, et al. The quality of clinical practice guidelines over the last two decades: a systematic review of guideline appraisal studies. Qual Saf Health Care. 2010;19:e58.

    PubMed  Google Scholar 

  13. Spieth PM, Kubasch AS, Penzlin AI, Illigens BM-W, Barlinn K, Siepmann T. Randomized controlled trials—a matter of design. Neuropsychiatr Dis Treat. 2016;12:1341.

    PubMed  PubMed Central  Google Scholar 

  14. Euser AM, Zoccali C, Jager KJ, Dekker FW. Cohort studies: prospective versus retrospective. Nephron Clin Pract. 2009;113:c214–7.

    Article  PubMed  Google Scholar 

  15. Weiss S, Silverman E, Palmer L. Case-control association studies in pharmacogenetics. Pharmacogenomics J. 2001;1:157–8.

    Article  CAS  PubMed  Google Scholar 

  16. van Aken J, Schmedders M, Feuerstein G, Kollek R. Prospects and Limits of Pharmacogenetics. Am J Pharmacogenomics. 2003;3:149–55.

    Article  PubMed  Google Scholar 

  17. van Schaik RH. Genetic techniques for pharmacogenetic analyses. Curr Pharm Des. 2010;16:231–7.

    Article  PubMed  Google Scholar 

  18. Gardiner SJ, Begg EJ. Pharmacogenetic testing for drug metabolizing enzymes: is it happening in practice? Pharmacogenetics Genom. 2005;15:365–9.

    Article  CAS  Google Scholar 

  19. Roses AD. Pharmacogenetics and the practice of medicine. Nature. 2000;405:857–65.

    Article  CAS  PubMed  Google Scholar 

  20. Al-Eitan LN, Jaradat SA, Su SY, Tay GK, Hulse GK. Mu opioid receptor (OPRM1) as a predictor of treatment outcome in opiate-dependent individuals of Arab descent. Pharmacogenomics Pers Med. 2012;5:99.

    CAS  Google Scholar 

  21. Hakooz N, Jarrar YB, Zihlif M, Imraish A, Hamed S, Arafat T. Effects of the genetic variants of organic cation transporters 1 and 3 on the pharmacokinetics of metformin in Jordanians. Drug Metab Pers Ther. 2017;32:157–62.

    CAS  PubMed  Google Scholar 

  22. Zalloum I, Hakooz N, Arafat T. Genetic polymorphism of CYP2C19 in a Jordanian population: influence of allele frequencies of CYP2C19* 1 and CYP2C19* 2 on the pharmacokinetic profile of lansoprazole. Mol Biol Rep. 2012;39:4195–200.

    Article  CAS  PubMed  Google Scholar 

  23. Yehya A, Irshaid Y, Abu Saleh A. Cholesteryl ester transfer protein rs1532624 gene polymorphism is associated with reduced response to statin therapy. Curr Mol Pharmacol. 2013;6:156–62.

    Article  CAS  PubMed  Google Scholar 

  24. Alzoubi KH, Khabour OF, Al-Azzam SI, Mayyas F, Mhaidat NM. The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians. Cytotechnology. 2015;67:267–74.

    Article  CAS  PubMed  Google Scholar 

  25. Abdullah S, Jarrar Y, Alhawari H, Hneet E, Zihlif M. The influence of endothelial nitric oxide synthase (Enos) genetic polymorphisms on cholesterol blood levels among type 2 diabetic patients on atorvastatin therapy. Endocr Metab Immune Disord Drug Targets. 2020;21:352–59.

  26. Jabr R, Gharaibeh M, Zayed AA, Zihlif M. The association between apolipoprotein E polymorphism and response to statins in group of hyperlipidemic patients. Endocr Metab Immune Disord Drug Targets. 2020.

  27. Al-Eitan LN, Almasri AY, Al-Habahbeh SO. Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease. Pharmacogenomics Pers Med. 2019;12:15.

    CAS  Google Scholar 

  28. Al-Eitan LN, Almasri AY, Al-Habahbeh SO. Effects of coagulation factor VII polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and maintenance phases of warfarin therapy. Pharmacogenomics Pers Med. 2019;12:1.

    CAS  Google Scholar 

  29. AL-Eitan LN, Almasri AY, Khasawneh RH. Impact of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation therapy. Genes. 2018;9:578.

    Article  PubMed Central  CAS  Google Scholar 

  30. Al-Azzam SI, Alzoubi KH, Khabour OF, Tawalbeh D, Al-Azzeh O. The contribution of platelet glycoproteins (GPIa C807T and GPIba C-5T) and cyclooxygenase 2 (COX-2G-765C) polymorphisms to platelet response in patients treated with aspirin. Gene. 2013;526:118–21.

    Article  CAS  PubMed  Google Scholar 

  31. Al-Azzam SI, Alzoubi KH, Khabour OF, Nusair MB, Al-Hadidi H, Awidi A, et al. Factors that contribute to clopidogrel resistance in cardiovascular disease patients: environmental and genetic approach. Int J Clin Pharmacol Ther. 2013;51:179–86.

    Article  CAS  PubMed  Google Scholar 

  32. Aneesh T, Sekhar S, Jose A, Chandran L, Zachariah SM. Pharmacogenomics: the right drug to the right person. J Clin Med Res. 2009;1:191.

    CAS  Google Scholar 

  33. Johnson JA. Drug target pharmacogenomics. Am J Pharmacogenomics. 2001;1:271–81.

    Article  CAS  PubMed  Google Scholar 

  34. Garten Y, Coulet A, Altman RB. Recent progress in automatically extracting information from the pharmacogenomic literature. Pharmacogenomics. 2010;11:1467–89.

    Article  PubMed  Google Scholar 

  35. Ernster VL. Nested case-control studies. Prev Med. 1994;23:587–90.

    Article  CAS  PubMed  Google Scholar 

  36. Roden DM, Wilke RA, Kroemer HK, Stein CM. Pharmacogenomics: the genetics of variable drug responses. Circulation. 2011;123:1661–70.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461:747–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hackshaw A. Small studies: strengths and limitations. Eur Respir Soc. 2008.

  39. Straw RB, Herrell JM. A framework for understanding and improving multisite evaluations. N Dir Eval. 2002;2002:5–16.

    Article  Google Scholar 

  40. Little J, Sharp L, Khoury MJ, Bradley L, Gwinn M. The epidemiologic approach to pharmacogenomics. Am J Pharmacogenomics. 2005;5:1–20.

    Article  CAS  PubMed  Google Scholar 

  41. Eisenberg RS. Will pharmacogenomics alter the role of patents in drug development? Pharmacogenomics. 2002;3:571–4.

    Article  PubMed  Google Scholar 

  42. Ingelman-Sundberg M. Pharmacogenomic biomarkers for prediction of severe adverse drug reactions. Mass Medical Soc. 2008.

  43. Monagle P, Chan AK, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Göttl U, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e737S–801S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Iqbal O. Pharmacogenomics in anticoagulant drug development. Pharmacogenomics. 2002;3:823–8.

    Article  CAS  PubMed  Google Scholar 

  45. Flowers CR, Veenstra D. The role of cost-effectiveness analysis in the era of pharmacogenomics. Pharmacoeconomics. 2004;22:481–93.

    Article  PubMed  Google Scholar 

  46. FDA Table of Pharmacogenomic Biomarkers in Drug Labeling. 2020. https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling.

  47. Al-Eitan LN, Al-Dalalah IM, Mustafa MM, Alghamdi MA, Elshammari AK, Khreisat WH, et al. Genetic polymorphisms of CYP3A5, CHRM2, and ZNF498 and their association with epilepsy susceptibility: a pharmacogenetic and case–control study. Pharmacogenomics Pers Med. 2019;12:225.

    CAS  Google Scholar 

  48. AL-Eitan LN, Al-Dalalah IM, Mustafa MM, Alghamdi MA, Elshammari AK, Khreisat WH, et al. Effects of MTHFR and ABCC2 gene polymorphisms on antiepileptic drug responsiveness in Jordanian epileptic patients. Pharmacogenomics Pers Med. 2019;12:87.

    CAS  Google Scholar 

  49. AL-Eitan LN, Al-Dalalah IM, Aljamal HA. Effects of GRM4, SCN2A and SCN3B polymorphisms on antiepileptic drugs responsiveness and epilepsy susceptibility. Saudi Pharm J. 2019;27:731–7.

    Article  PubMed  PubMed Central  Google Scholar 

  50. AL-Eitan LN, Al-Dalalah IM, Elshammari AK, Khreisat WH, Almasri AY. The impact of potassium channel gene polymorphisms on antiepileptic drug responsiveness in Arab patients with epilepsy. J Pers Med. 2018;8:37.

    Article  PubMed Central  Google Scholar 

  51. Sakai T, Aoyama N, Kita T, Sakaeda T, Nishiguchi K, Nishitora Y, et al. CYP2C19 genotype and pharmacokinetics of three proton pump inhibitors in healthy subjects. Pharm Res. 2001;18:721–7.

    Article  CAS  PubMed  Google Scholar 

  52. Román M, Ochoa D, Sánchez-Rojas SD, Talegón M, Prieto-Pérez R, Rivas Â, et al. Evaluation of the relationship between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole, pantoprazole and rabeprazole. Pharmacogenomics. 2014;15:1893–901.

    Article  PubMed  CAS  Google Scholar 

  53. Lay C-S, Lin J-R. Correlation of CYP2C19 genetic polymorphisms with helicobacter pylori eradication in patients with cirrhosis and peptic ulcer. J Chin Med Assoc. 2010;73:188–93.

    Article  CAS  PubMed  Google Scholar 

  54. Ram MR, Teh X, Rajakumar T, Goh KL, Leow AHR, Poh BH, et al. Polymorphisms in the host CYP2C19 gene and antibiotic-resistance attributes of Helicobacter pylori isolates influence the outcome of triple therapy. J Antimicrobial Chemother. 2019;74:11–6.

    Article  CAS  Google Scholar 

  55. Al-Eitan LN, Jaradat SA, Qin W, Wildenauer DMB, Wildenauer DD, Hulse GK, et al. Characterization of serotonin transporter gene (SLC6A4) polymorphisms and its association with drug dependence in a Jordanian Arab population. Toxicol Ind Health. 2014;30:598–610.

    Article  PubMed  CAS  Google Scholar 

  56. Lin P-Y, Wu Y-S. Association between serotonin transporter gene polymorphisms and heroin dependence: a meta-analytic study. Neuropsychiatr Dis Treat. 2016;12:3061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Porcelli S, Fabbri C, Serretti A. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol. 2012;22:239–58.

    Article  CAS  PubMed  Google Scholar 

  58. Milovanovic DD, Radosavljevic I, Radovanovic M, Milovanovic JR, Obradovic S, Jankovic S, et al. CYP3A5 polymorphism in serbian paediatric epileptic patients on carbamazepine treatment. Serb J Exp Clin Res. 2015;16:93–9.

    Article  CAS  Google Scholar 

  59. Meng H, Guo G, Ren J, Zhou H, Ge Y, Guo Y. Effects of ABCB1 polymorphisms on plasma carbamazepine concentrations and pharmacoresistance in Chinese patients with epilepsy. Epilepsy Behav. 2011;21:27–30.

    Article  PubMed  Google Scholar 

  60. Gambano G, Anglani F, D’Angelo A. Association studies of genetic polymorphisms and complex disease. Lancet. 2000;355:308–11.

    Article  Google Scholar 

  61. Zhao X, Huang Y, Li J, Ma H, Jin Q, Wang Y, et al. Association between the 5-HT1A receptor gene polymorphism (rs6295) and antidepressants: a meta-analysis. Int Clin Psychopharmacol. 2012;27:314–20.

    PubMed  Google Scholar 

  62. Taylor MJ, Sen S, Bhagwagar Z. Antidepressant response and the serotonin transporter gene-linked polymorphic region. Biol Psychiatry. 2010;68:536–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Nazer LH, Tuffaha H. Health care and pharmacy practice in Jordan. Can J Hosp Pharm. 2017;70:150.

    PubMed  PubMed Central  Google Scholar 

  64. Dardas LA, Silva SG, Smoski MJ, Noonan D, Simmons LA. The prevalence of depressive symptoms among Arab adolescents: findings from Jordan. Public Health Nurs. 2018;35:100–8.

    Article  PubMed  Google Scholar 

  65. Rasmieh A-A, Subih M, Aldaraawi H, Randall S, Othman WMM, Salamonson Y. Prevalence of depression and its influence on the quality of life of Jordanians living in residential care facilities. J Nurs Res. 2019;27:e54.

    Article  Google Scholar 

  66. Malak MZ, Khalifeh AH. Anxiety and depression among school students in Jordan: Prevalence, risk factors, and predictors. Perspect Psychiatr Care. 2018;54:242–50.

    Article  PubMed  Google Scholar 

  67. Okasha A, Karam E, Okasha T. Mental health services in the Arab world. World Psychiatry. 2012;11:52–4.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Eiland LS, Luttrell PK. Use of statins for dyslipidemia in the pediatric population. J Pediatr Pharmacol Ther. 2010;15:160–72.

    PubMed  PubMed Central  Google Scholar 

  69. Hedman M, Antikainen M, Holmberg C, Neuvonen M, Eichelbaum M, Kivistö KT, et al. Pharmacokinetics and response to pravastatin in paediatric patients with familial hypercholesterolaemia and in paediatric cardiac transplant recipients in relation to polymorphisms of the SLCO1B1 and ABCB1 genes. Br J Clin Pharmacol. 2006;61:706–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wagner JB, Abdel‐Rahman S, Gaedigk A, Gaedigk R, Raghuveer G, Staggs VS, et al. Impact of SLCO1B1 genetic variation on rosuvastatin systemic exposure in pediatric hypercholesterolemia. Clin Transl Sci. 2020;13:628–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Johnson PK, Mendelson MM, Baker A, Ryan HH, Warren S, Graham D, et al. Statin-associated myopathy in a pediatric preventive cardiology practice. J Pediatr. 2017;185:94–8.e1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Weinshilboum R, Wang L. Pharmacogenomics: bench to bedside. Nat Rev Drug Discov. 2004;3:739–48.

    Article  CAS  PubMed  Google Scholar 

  73. Jordan News Agency, Petra. The Jordan Times. JD42m spent on scientific research in 10 years. 2018. Available: https://www.jordantimes.com/news/local/jd42m-spent-scientific-research-10-years.

  74. Caudle KE, Klein TE, Hoffman JM, Muller DJ, Whirl-Carrillo M, Gong L, et al. Incorporation of pharmacogenomics into routine clinical practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline development process. Curr Drug Metab. 2014;15:209–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. PhD. Pharmacology - Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan

    Alaa Yehya

  2. PhD. Biotechnology - Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan

    Zaid Altaany

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Study design: AY. Data collection and interpretation: AY, ZA. Drafting paper: AY. Revising paper content: ZA. All authors approved the final version of the paper.

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Correspondence to Alaa Yehya.

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Yehya, A., Altaany, Z. A Decade of Pharmacogenetic Studies in Jordan: A Systemic Review. Pharmacogenomics J 21, 543–550 (2021). https://doi.org/10.1038/s41397-021-00236-6

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