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Pharmaceutical Research

, 35:211 | Cite as

Genetic Basis of Delayed Hypersensitivity Reactions to Drugs in Jewish and Arab Populations

  • Mohammed Aboukaoud
  • Shoshana Israel
  • Chaim Brautbar
  • Sara EyalEmail author
Expert Review
  • 171 Downloads

Abstract

Genetic variation can affect drug pharmacokinetics and pharmacodynamics and contribute to variability between individuals in response to medications. Specifically, differences in allele frequencies among individuals and ethnic groups have been associated with variation in their propensity to develop drug hypersensitivity reactions (HSRs). This article reviews the current knowledge on the genetic background of HSRs and its relevance to Jewish and Arab populations. The focus is on human leukocyte antigen (HLA) alleles and haplotypes as predictive markers of HSRs (“immunopharmacogenetics”), but other genes and alleles are described as well. Also discussed is the translation of the pharmacogenetic information to practice recommendations.

KEY WORDS

Arab human leukocyte antigens hypersensitivity reactions Jewish 

ABBREVIATIONS

ALT

Alanine aminotransferase

CYP

Cytochrome P450

DILI

Drug-induced liver injury

DRESS

Drug reaction with eosinophilia and systemic symptoms

EMA

European Medicines Agency

FDA

Food and Drug Administration

G6PD

Glucose 6-phosphate dehydrogenase

GME

Greater Middle East

HLA

Human leukocyte antigen

HSR

Hypersensitivity reaction

MHC

Major histocompatibility complex

NMDP

National Marrow Donor Program

SCAR

Severe cutaneous adverse drug reactions

SJS

Stevens-Johnson syndrome

TEN

Toxic epidermal necrolysis

TPMT

Thiopurine S-methyltransferase

Notes

Acknowledgments and Disclosures

This work was supported by funding from the Hebrew University’s School of Pharmacy. Sara Eyal is affiliated with the David R. Bloom Centre for Pharmacy and Dr. Adolf and Klara Brettler Center at The Hebrew University of Jerusalem, Israel.

References

  1. 1.
    Demoly P, Adkinson NF, Brockow K, Castells M, Chiriac AM, Greenberger PA, et al. International consensus on drug allergy. Allergy. 2014;69:420–37.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Pavlos R, Mallal S, Ostrov D, Buus S, Metushi I, Peters B, et al. T cell-mediated hypersensitivity reactions to drugs. Annu Rev Med. 2015;66:439–54.PubMedCrossRefGoogle Scholar
  3. 3.
    Pirmohamed M, Ostrov DA, Park BK. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity. J Allergy Clin Immunol. 2015;136:236–44.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Uetrecht J, Naisbitt DJ. Idiosyncratic adverse drug reactions: current concepts. Pharmacol Rev. 2013;65:779–808.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Phillips EJ. Classifying ADRs--does dose matter? Br J Clin Pharmacol. 2016;81:10–2.PubMedCrossRefGoogle Scholar
  6. 6.
    Bharadwaj M, Illing P, Theodossis A, Purcell AW, Rossjohn J, McCluskey J. Drug hypersensitivity and human leukocyte antigens of the major histocompatibility complex. Annu Rev Pharmacol Toxicol. 2012;52:401–31.PubMedCrossRefGoogle Scholar
  7. 7.
    Amstutz U, Shear NH, Rieder MJ, Hwang S, Fung V, Nakamura H, et al. Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions. Epilepsia. 2014;55:496–506.PubMedCrossRefGoogle Scholar
  8. 8.
    Yang Y, Peter I, Scott SA. Pharmacogenetics in Jewish populations. Drug Metabol Drug Interact. 2014;29:221–33.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Dagenais R, Wilby KJ, Elewa H, Ensom MHH. Impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in the Middle East and North Africa region. Drugs R D. 2017;17:341–61.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Ossaily S, Zgheib NK. The pharmacogenetics of drug metabolizing enzymes in the Lebanese population. Drug Metabol Drug Interact. 2014;29:81–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Lucena MI, Molokhia M, Shen Y, Urban TJ, Aithal GP, Andrade RJ, et al. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011;141:338–47.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Caudle KE, Rettie AE, Whirl-Carrillo M, Smith LH, Mintzer S, Lee MT, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther. 2014;96:542–8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Hershfield MS, Callaghan JT, Tassaneeyakul W, Mushiroda T, Thorn CF, Klein TE, et al. Clinical pharmacogenetics implementation consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93:153–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Saito Y, Stamp LK, Caudle KE, Hershfield MS, McDonagh EM, Callaghan JT, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update. Clin Pharmacol Ther. 2016;99:36–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Leckband SG, Kelsoe JR, Dunnenberger HM, George AL, Tran E, Berger R, et al. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther. 2013;94:324–8.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Martin MA, Hoffman JM, Freimuth RR, Klein TE, Dong BJ, Pirmohamed M, et al. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and Abacavir dosing: 2014 update. Clin Pharmacol Ther. 2014;95:499–500.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Schnyder B, Brockow K. Pathogenesis of drug allergy--current concepts and recent insights. Clin Exp Allergy. 2015;45:1376–83.PubMedCrossRefGoogle Scholar
  18. 18.
    Torres MJ, Salas M, Ariza A, Fernández TD. Understanding the mechanisms in accelerated drug reactions. Curr Opin Allergy Clin Immunol. 2016;16:308–14.PubMedCrossRefGoogle Scholar
  19. 19.
    SZEINBERG A, OLIVER M, SCHMIDT R, ADAM A, SHEBA C. Glucose-6-phosphate dehydrogenase deficiency and haemolytic disease of the newborn in Israel. Arch Dis Child. 1963;38:23–8.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Amar A, Kwon OJ, Motro U, Witt CS, Bonne-Tamir B, Gabison R, et al. Molecular analysis of HLA class II polymorphisms among different ethnic groups in Israel. Hum Immunol. 1999;60:723–30.PubMedCrossRefGoogle Scholar
  21. 21.
    Bonné-Tamir B, Bodmer JG, Bodmer WF, Pickbourne P, Brautbar C, Gazit E, et al. HLA polymorphism in Israel. 9. An overall comparative analysis. Tissue Antigens. 1978;11:235–50.PubMedCrossRefGoogle Scholar
  22. 22.
    Cohen T, Levene C, Yodfat Y, Fidel J, Friedlander Y, Steinberg AG, et al. Genetic studies on cochin Jews in Israel: 1. Population data, blood groups, isoenzymes, and HLA determinants. Am J Med Genet. 1980;6:61–73.PubMedCrossRefGoogle Scholar
  23. 23.
    Karlin S, Kenett R, Bonné-Tamir B. Analysis of biochemical genetic data on Jewish populations: II. Results and interpretations of heterogeneity indices and distance measures with respect to standards. Am J Hum Genet. 1979;31:341–65.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Klitz W, Gragert L, Maiers M, Fernandez-Viña M, Ben-Naeh Y, Benedek G, et al. Genetic differentiation of Jewish populations. Tissue Antigens. 2010;76:442–58.PubMedCrossRefGoogle Scholar
  25. 25.
    Manor S, Halagan M, Shriki N, Yaniv I, Zisser B, Maiers M, et al. High-resolution HLA a approximately B approximately DRB1 haplotype frequencies from the Ezer Mizion bone marrow donor registry in Israel. Hum Immunol. 2016;77:1114–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Evron E, Brautbar C, Becker S, Fenakel G, Abend Y, Sthoeger Z, et al. Correlation between gold-induced enterocolitis and the presence of the HLA-DRB1*0404 allele. Arthritis Rheum. 1995;38:755–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Matzner Y, Erlich HA, Brautbar C, Sanilevitch A, Landau M, Brenner S, et al. Identical HLA class II alleles predispose to drug-triggered and idiopathic pemphigus vulgaris. Acta Derm Venereol. 1995;75:12–4.PubMedGoogle Scholar
  28. 28.
    Gonzalez-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, da Silva AL, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res. 2015;28:D784–8.CrossRefGoogle Scholar
  29. 29.
    National Marrow Donor Program (US). Jewish High-Resolution Haplotype Frequencies. https://bioinformatics.bethematchclinical.org/hla-resources/haplotype-frequencies/jewish-high-resolution-haplotype-frequencies/ accessed April 28 2018.
  30. 30.
    Ostrer H. A genetic profile of contemporary Jewish populations. Nat Rev Genet. 2001;2:891–8.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Atzmon G, Hao L, Pe'er I, Velez C, Pearlman A, Palamara PF, et al. Abraham's children in the genome era: major Jewish diaspora populations comprise distinct genetic clusters with shared middle eastern ancestry. Am J Hum Genet. 2010;86:850–9.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Behar DM, Yunusbayev B, Metspalu M, Metspalu E, Rosset S, Parik J, et al. The genome-wide structure of the Jewish people. Nature. 2010;466:238–42.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Carmi S, Hui KY, Kochav E, Liu X, Xue J, Grady F, et al. Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins. Nat Commun. 2014;5:4835.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Kopelman NM, Stone L, Wang C, Gefel D, Feldman MW, Hillel J, et al. Genomic microsatellites identify shared Jewish ancestry intermediate between middle eastern and European populations. BMC Genet. 2009;10:1–14.CrossRefGoogle Scholar
  35. 35.
    Ostrer H, Skorecki K. The population genetics of the Jewish people. Hum Genet. 2013;132:119–27.PubMedCrossRefGoogle Scholar
  36. 36.
    Chaubey G, Singh M, Rai N, Kariappa M, Singh K, Singh A, et al. Genetic affinities of the Jewish populations of India. Sci Rep. 2016;6:19166.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Waldman YY, Biddanda A, Davidson NR, Billing-Ross P, Dubrovsky M, Campbell CL, et al. The genetics of bene Israel from India reveals both substantial Jewish and Indian ancestry. PLoS One. 2016;11:e0152056.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Steinberg AG, Levene C, Yodfat Y, Fidel J, Brautbar C, Cohen T. Genetic studies on cochin Jews in Israel: 2. Gm and Inv data--polymorphism for Gm3 and for Gm1,17,21 without gm(26). Am J Med Genet. 1980;6:75–81.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Scott EM, Halees A, Itan Y, Spencer EG, He Y, Azab MA, et al. Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery. Nat Genet. 2016;advance online publication;48:1071–6.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Haber M, Gauguier D, Youhanna S, Patterson N, Moorjani P, Botigué LR, et al. Genome-wide diversity in the levant reveals recent structuring by culture. PLoS Genet. 2013;9:e1003316.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Hellenthal G, Busby GB, Band G, Wilson JF, Capelli C, Falush D, et al. A genetic atlas of human admixture history. Science. 2014;343:747–51.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Hajjej A, Almawi WY, Arnaiz-Villena A, Hattab L, Hmida S. The genetic heterogeneity of Arab populations as inferred from HLA genes. PLoS One. 2018;13:e0192269.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Bishara A, Brautbar C, Israel S, Halagan M, Madbouly A, Fernandez Vina M, et al. HLA allele and haplotype frequencies for Christian and Muslim Arab donors in Hadassah (meeting abstract). Hum Immunol. 2013;74(Suppl):51–173.Google Scholar
  44. 44.
    Li JZ, Absher DM, Tang H, Southwick AM, Casto AM, Ramachandran S, et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science. 2008;319:1100–4.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Zidan J, Ben-Avraham D, Carmi S, Maray T, Friedman E, Atzmon G. Genotyping of geographically diverse Druze trios reveals substructure and a recent bottleneck. Eur J Hum Genet. 2015;23:1093–9.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Brautbar C, Israel S, Firro K. Population: Arab Druse from Israel. In: Mack SJ, Tsai Y, Sanchez-Mazas A, Erlich HA, editors. 13th International Histocompatibility Workshop Anthropology/Human Genetic Diversity Joint Report Chapter 3: Anthropology/human genetic diversity population reports 2006.Google Scholar
  47. 47.
    Ronen O, Cohen SB, Rund D. Evaluating frequencies of thiopurine S-methyl transferase (TPMT) variant alleles in Israeli ethnic subpopulations using DNA analysis. Isr Med Assoc J. 2010;12:721–5.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Efrati E, Elkin H, Sprecher E, Krivoy N. Distribution of CYP2C9 and VKORC1 risk alleles for warfarin sensitivity and resistance in the Israeli population. Curr Drug Saf. 2010;5:190–3.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    MJB Data Snapshot: The Bedouin in Israel. The Myers-JDC-Brookdale Institute; 2017. Available at: https://brookdale.jdc.org.il/wp-content/uploads/2018/01/MJB-Data-Snapshot-The-Bedouin-in-Israel-May-2017-FINAL.pdf. Accessed 2 Sept 2018.Google Scholar
  50. 50.
    Rosner G, Rosner S, Orr-Urtreger A. Genetic testing in Israel: an overview. Annu Rev Genomics Hum Genet. 2009;10:175–92.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002;359:1121–2.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359:727–32.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I, Floratos A, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009;41:816–9.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Clay PG. The abacavir hypersensitivity reaction: a review. Clin Ther. 2002;24:1502–14.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358:568–79.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Saag M, Balu R, Phillips E, Brachman P, Martorell C, Burman W, et al. High sensitivity of human leukocyte antigen-B*5701 as a marker for immunologically confirmed Abacavir hypersensitivity in white and black patients. Clin Infect Dis. 2008;46:1111–8.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Redwood AJ, Pavlos RK, White KD, Phillips EJ. HLAs: key regulators of T-cell-mediated drug hypersensitivity. HLA. 2018;91:3–16.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Plumpton CO, Roberts D, Pirmohamed M, Hughes DA. A systematic review of economic evaluations of pharmacogenetic testing for prevention of adverse drug reactions. PharmacoEconomics. 2016;34:771–93.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Ruiz-Iruela C, Padullés-Zamora N, Podzamczer-Palter D, Alonso-Pastor A, Candás-Estébanez B, Alía-Ramos P, et al. HLA-B*57: 01 genotyping in the prevention of hypersensitivity to abacavir: 5 years of experience. Pharmacogenet Genomics. 2016;26:390–6.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    U.S. Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling. http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm. Last Updated: 07/11/2016. Accessed August 9 2016.
  61. 61.
    European Medicines Agency. http://www.ema.europa.eu/ema/. Accessed August 9 2016. 2016.
  62. 62.
    Israel S, Maggio N, Ekstein D, Zaid H, Firer M, Bederovsky Y, et al. Genetic risk factors for antiepileptic drug-induced hypersensitivity reactions in Israeli populations. Epilepsia. 2016;57:205–e9.CrossRefGoogle Scholar
  63. 63.
    Wozel VE. Innovative use of dapsone. Dermatol Clin. 2010;28:599–610.PubMedCrossRefGoogle Scholar
  64. 64.
    Lorenz M, Wozel G, Schmitt J. Hypersensitivity reactions to dapsone: a systematic review. Acta Derm Venereol. 2012;92:194–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Zhang FR, Liu H, Irwanto A, Fu XA, Li Y, Yu GQ, et al. HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med. 2013;369:1620–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Tangamornsuksan W, Lohitnavy M. Association between HLA-B*1301 and Dapsone-induced cutaneous adverse drug reactions: a systematic review and meta-analysis. JAMA Dermatol. 2018;154:441–6.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Sanchez-Velasco P, Karadsheh NS, Garcia-Martin A, Ruiz de Alegria C, Leyva-Cobian F. Molecular analysis of HLA allelic frequencies and haplotypes in Jordanians and comparison with other related populations. Hum Immunol. 2001;62:901–9.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Drug Allergies. http://www.worldallergy.org/professional/allergic_diseases_center/drugallergy/ Last updated 2014. Accessed August 4 2016.
  69. 69.
    Rzany B, Mockenhaupt M, Baur S, Schroder W, Stocker U, Mueller J. Epidemiology of erythema exsudativum multiforme majus (EEMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Germany (1990-1992). Structure and results of a population based registry. J Clin Epidemiol. 1996;49:769–73.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Halevy S, Ghislain P-D, Mockenhaupt M, Fagot J-P, Bouwes Bavinck JN, Sidoroff A, et al. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol. 2008;58:25–32.PubMedCrossRefGoogle Scholar
  71. 71.
    Maggio N, Firer M, Zaid H, Bederovsky Y, Aboukaoud M, Gandelman-Marton R, et al. Causative drugs of Stevens-Johnson syndrome and toxic epidermal necrolysis in Israel. J Clin Pharmacol. 2017;57:823–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004;428:486.PubMedCrossRefGoogle Scholar
  73. 73.
    Locharernkul C, Loplumlert J, Limotai C, Korkij W, Desudchit T, Tongkobpetch S, et al. Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008;49:2087–91.PubMedCrossRefGoogle Scholar
  74. 74.
    Khor AH, Lim KS, Tan CT, Wong SM, Ng CC. HLA-B*15:02 association with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in an Indian population: a pooled-data analysis and meta-analysis. Epilepsia. 2014;55:e120–4.PubMedCrossRefGoogle Scholar
  75. 75.
    Bloch KM, Sills GJ, Pirmohamed M, Alfirevic A. Pharmacogenetics of antiepileptic drug-induced hypersensitivity. Pharmacogenomics. 2014;15:857–68.PubMedCrossRefGoogle Scholar
  76. 76.
    Tangamornsuksan W, Chaiyakunapruk N, Somkrua R, Lohitnavy M, Tassaneeyakul W. Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol. 2013;149:1025–32.PubMedCrossRefGoogle Scholar
  77. 77.
    Yip VL, Marson AG, Jorgensen AL, Pirmohamed M, Alfirevic A. HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a systematic review. Clin Pharmacol Ther. 2012;92:757–65.PubMedCrossRefGoogle Scholar
  78. 78.
    Chen P, Lin JJ, Lu CS, Ong CT, Hsieh PF, Yang CC, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364:1126–33.PubMedCrossRefGoogle Scholar
  79. 79.
    McCormack M, Alfirevic A, Bourgeois S. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011;364:1134–43.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Ozeki T, Mushiroda T, Yowang A, Takahashi A, Kubo M, Shirakata Y, et al. Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum Mol Genet. 2011;20:1034–41.PubMedCrossRefGoogle Scholar
  81. 81.
    Kim SH, Lee KW, Song WJ, Kim SH, Jee YK, Lee SM, et al. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res. 2011;97:190–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Ghattaoraya GS, Dundar Y, González-Galarza FF, Maia MH, Santos EJ, da Silva AL, et al. A web resource for mining HLA associations with adverse drug reactions: HLA-ADR. Database (Oxford) 2016, 2016.Google Scholar
  83. 83.
    Jaruthamsophon K, Tipmanee V, Sangiemchoey A, Sukasem C, Limprasert P. HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis. Sci Rep. 2017;7:45553.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui RC, et al. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010;11:349–56.PubMedCrossRefGoogle Scholar
  85. 85.
    Man CB, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia. 2007;48:1015–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Information for Healthcare Professionals: Phenytoin (marketed as Dilantin, Phenytek and generics) and Fosphenytoin Sodium (marketed as Cerebyx and generics). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124788.htm Last Updated: 23 August 2013. Accessed 9 August 2016.
  87. 87.
    Cheung YK, Cheng SH, Chan EJ, Lo SV, Ng MH, Kwan P. HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013;54:1307–14.PubMedCrossRefGoogle Scholar
  88. 88.
    Shi YW, Min FL, Zhou D, Qin B, Wang J, Hu FY, et al. HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions. Neurology. 2017;88:2183–91.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Sassolas B, Haddad C, Mockenhaupt M, Dunant A, Liss Y, Bork K, et al. ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharmacol Ther. 2010;88:60–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Firer M, Bederovsky Y, Maggio N. Eyal S. SJS/TEN in Jewish and Arab populations: Epilepsia 2018;59:1469–70.Google Scholar
  91. 91.
    Israel Central Bureau of Statistics. Jews, by country of origin (1) and age. Average 2016. http://www.cbs.gov.il/shnaton68/st02_08x.pdf Published September 6 2017. Accessed May 5 2018. .
  92. 92.
    Mandel MS. Muslims and Jews in France. History of a Conflict. Princeton: Princeton University Press; 2014.  https://doi.org/10.1017/S0364009414000531.CrossRefGoogle Scholar
  93. 93.
    Tassaneeyakul W, Prabmeechai N, Sukasem C, Kongpan T, Konyoung P, Chumworathayi P, et al. Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population. Pharmacogenet Genomics. 2016;26:225–34.PubMedCrossRefGoogle Scholar
  94. 94.
    Nakai K, Habano W, Nakai K, Fukushima N, Suwabe A, Moriya S, et al. Ethnic differences in CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes in Japanese and Israeli populations. Life Sci. 2005;78:107–11.PubMedCrossRefGoogle Scholar
  95. 95.
    Ayesh BM, Abu Shaaban AS, Abed AA. Evaluation of CYP2C9- and VKORC1-based pharmacogenetic algorithm for warfarin dose in Gaza-Palestine. Future Sci OA. 2018;4:Fso276.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Bader LA, Elewa H. The impact of genetic and non-genetic factors on warfarin dose prediction in MENA region: a systematic review. PLoS One. 2016;11:e0168732.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005;102:4134–9.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Génin E, Schumacher M, Roujeau JC, Naldi L, Liss Y, Kazma R, et al. Genome-wide association study of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe. Orphanet J Rare Dis. 2011;6:52.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, et al. A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics. 2008;18:99–107.PubMedCrossRefGoogle Scholar
  100. 100.
    Barbarino JM, Kroetz DL, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for human leukocyte antigen B. Pharmacogenet Genomics. 2015;25:205–21.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Lu N, Rai SK, Terkeltaub R, Kim SC, Menendez ME, Choi HK. Racial disparities in the risk of Stevens-Johnson Syndrome and toxic epidermal necrolysis as urate-lowering drug adverse events in the United States. Semin Arthritis Rheum. 2016;46:253–8.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Ko TM, Tsai CY, Chen SY, Chen KS, Yu KH, Chu CS, et al. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ. 2015;351:h4848.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Kongpan T, Mahasirimongkol S, Konyoung P, Kanjanawart S, Chumworathayi P, Wichukchinda N, et al. Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions. Pharmacogenet Genomics. 2015;25:402–11.PubMedCrossRefGoogle Scholar
  104. 104.
    FDA advises against using oral ketoconazole in drug interaction studies due to serious potential side effects. http://www.fda.gov/Drugs/DrugSafety/ucm371017.htm Last Updated: October 14 2015. Accessed August 11 2016. .
  105. 105.
    Daly AK. Using genome-wide association studies to identify genes important in serious adverse drug reactions. Annu Rev Pharmacol Toxicol. 2012;52:21–35.PubMedCrossRefGoogle Scholar
  106. 106.
    Kim SH, Naisbitt DJ. Update on advances in research on idiosyncratic drug-induced liver injury. Allergy, Asthma Immunol Res. 2016;8:3–11.CrossRefGoogle Scholar
  107. 107.
    Donaldson PT, Daly AK, Henderson J, Graham J, Pirmohamed M, Bernal W, et al. Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury. J Hepatol. 2010;53:1049–53.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Hautekeete ML, Horsmans Y, van Waeyenberge C, Demanet C, Henrion J, Verbist L, et al. HLA association of amoxicillin-clavulanate–induced hepatitis. Gastroenterology. 1999;117:1181–6.PubMedCrossRefGoogle Scholar
  109. 109.
    O'Donohue J, Oien KA, Donaldson P, Underhill J, Clare M, MacSween RN, et al. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut. 2000;47:717–20.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med. 2005;353:172–87.PubMedCrossRefGoogle Scholar
  111. 111.
    Xu CF, Johnson T, Wang X, Carpenter C, Graves AP, Warren L, et al. HLA-B*57:01 confers susceptibility to Pazopanib-associated liver injury in patients with Cancer. Clin Cancer Res. 2016;22:1371–7.PubMedCrossRefGoogle Scholar
  112. 112.
    Schaid DJ, Spraggs CF, McDonnell SK, Parham LR, Cox CJ, Ejlertsen B, et al. Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury. J Clin Oncol. 2014;32:2296–303.PubMedCrossRefGoogle Scholar
  113. 113.
    Spraggs CF, Budde LR, Briley LP, Bing N, Cox CJ, King KS, et al. HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer. J Clin Oncol. 2011;29:667–73.PubMedCrossRefGoogle Scholar
  114. 114.
    Roitberg-Tambur A, Witt CS, Friedmann A, Safirman C, Sherman L, Battat S, et al. Comparative analysis of HLA polymorphism at the serologic and molecular level in Moroccan and Ashkenazi Jews. Tissue Antigens. 1995;46:104–10.PubMedCrossRefGoogle Scholar
  115. 115.
    Kindmark A, Jawaid A, Harbron CG, Barratt BJ, Bengtsson OF, Andersson TB, et al. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharm J. 2008;8:186–95.Google Scholar
  116. 116.
    Carr DF, Chaponda M, Jorgensen AL, Castro EC, van Oosterhout JJ, Khoo SH, et al. Association of human leukocyte antigen alleles and nevirapine hypersensitivity in a Malawian HIV-infected population. Clin Infect Dis. 2013;56:1330–9.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Martis S, Mei H, Vijzelaar R, Edelmann L, Desnick RJ, Scott SA. Multi-ethnic cytochrome-P450 copy number profiling: novel pharmacogenetic alleles and mechanism of copy number variation formation. Pharm J. 2013;13:558–66.Google Scholar
  118. 118.
    Urban TJ, Shen Y, Stolz A, Chalasani N, Fontana RJ, Rochon J, et al. Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs. Pharmacogenet Genomics. 2012;22:784–95.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, et al. Association of Liver Injury from Specific Drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study. Gastroenterology. 2017;152:1078–89.PubMedCrossRefGoogle Scholar
  120. 120.
    Bhatt V, Saleem A. Review: drug-induced neutropenia--pathophysiology, clinical features, and management. Ann Clin Lab Sci. 2004;34:131–7.PubMedGoogle Scholar
  121. 121.
    Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007;146:657–65.PubMedCrossRefGoogle Scholar
  122. 122.
    Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993;329:162–7.PubMedCrossRefGoogle Scholar
  123. 123.
    Atkin K, Kendall F, Gould D, Freeman H, Liberman J, O'Sullivan D. Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland. Br J Psychiatry. 1996;169:483–8.PubMedCrossRefGoogle Scholar
  124. 124.
    Price KO. Ethnicity and clozapine-induced agranulocytosis. Clin Pharm. 1991;10:743–4.PubMedGoogle Scholar
  125. 125.
    Lieberman JA, Yunis J, Egea E, Canoso RT, Kane JM, Yunis EJ. HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. Arch Gen Psychiatry. 1990;47:945–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Yunis JJ, Corzo D, Salazar M, Lieberman JA, Howard A, Yunis EJ. HLA associations in clozapine-induced agranulocytosis. Blood. 1995;86:1177–83.PubMedGoogle Scholar
  127. 127.
    Valevski A, Klein T, Gazit E, Meged S, Stein D, Elizur A, et al. HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients. Eur J Immunogenet. 1998;25:11–3.PubMedCrossRefGoogle Scholar
  128. 128.
    Meged S, Stein D, Sitrota P, Melamed Y, Elizur A, Shmuelian I, et al. Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced agranulocytosis in jewish Israeli schizophrenic patients. Int Clin Psychopharmacol. 1999;14:305–12.PubMedCrossRefGoogle Scholar
  129. 129.
    Goldstein JI, Fredrik Jarskog L, Hilliard C, Alfirevic A, Duncan L, Fourches D, et al. Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. Nat Commun. 2014;5:4757.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Nakamura H, Miyauchi A, Miyawaki N, Imagawa J. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. J Clin Endocrinol Metab. 2013;98:4776–83.PubMedCrossRefGoogle Scholar
  131. 131.
    Tajiri J, Noguchi S. Antithyroid drug-induced agranulocytosis: special reference to normal white blood cell count agranulocytosis. Thyroid. 2004;14:459–62.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Chen PL, Shih SR, Wang PW, Lin YC, Chu CC, Lin JH, et al. Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Nat Commun. 2015;6:7633.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Cheung CL, Sing CW, Tang C, Cheng V, Pirmohamed M, Choi CH, et al. HLA-B*38:02:01 predicts carbimazole/methimazole-induced agranulocytosis. Clin Pharmacol Ther. 2016;99:555–61.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Hallberg P, Eriksson N, Ibañez L, Bondon-Guitton E, Kreutz R, Carvajal A, et al. Genetic variants associated with antithyroid drug-induced agranulocytosis: a genome-wide association study in a European population. Lancet Diabetes Endocrinol. 2016;4:507–16.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Hearn L, Derry S, Moore RA. Single dose dipyrone (metamizole) for acute postoperative pain in adults. Cochrane Database Syst Rev. 2016;20:CD011421.Google Scholar
  136. 136.
    Moore RA, Wiffen PJ, Derry S, Maguire T, Roy YM, Tyrrell L. Non-prescription (OTC) oral analgesics for acute pain - an overview of Cochrane reviews. Cochrane Database Syst Rev. 2015:CD010794.  https://doi.org/10.1002/14651858.CD010794.pub2.
  137. 137.
    Levy M. Hypersensitivity to pyrazolones. Thorax. 2000;55:S72–4.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    The Israel Ministry of Health. The Israel Drug registry. http://www.old.health.gov.il/units/pharmacy/trufot/index.asp?safa=e Last updated Access date 25 May 2017.
  139. 139.
    Kötter T, da Costa BR, Fässler M, Blozik E, Linde K, Jüni P, et al. Metamizole-associated adverse events: a systematic review and meta-analysis. PLoS One. 2015;10:e0122918.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Bhaumik S. India's health ministry bans pioglitazone, metamizole, and flupentixol-melitracen. BMJ. 2013;347:f4366.PubMedCrossRefPubMedCentralGoogle Scholar
  141. 141.
    Nikolova I, Petkova V, Tencheva J, Benbasat N, Voinikov J, Danchev N. Metamizole: a review profile of a well-known “forgotten” drug. Part II: clinical profile. Biotechnol Biotechnol Eq. 2013;27:3605–19.CrossRefGoogle Scholar
  142. 142.
    Discombe G. Agranulocytosis caused by amidopyrine; an avoidable cause of death. Br Med J. 1952;1:1270–3.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Huguley CM. Agranolocytosis induced by dipyrone, a hazardous antipyretic and analgesic. JAMA. 1964;189:938–41.PubMedCrossRefGoogle Scholar
  144. 144.
    Böttiger LE, Westerholm B. Drug-induced blood dyscrasias in Sweden. Br Med J. 1973;3:339–43.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol. 2002;58:265–74.PubMedCrossRefGoogle Scholar
  146. 146.
    Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study. JAMA. 1986;256:1749–57.CrossRefGoogle Scholar
  147. 147.
    Vlahov V, Bacracheva N, Tontcheva D, Naumova E, Mavrudieva M, Ilieva P, et al. Genetic factors and risk of agranulocytosis from metamizol. Pharmacogenetics. 1996;6:67–72.PubMedCrossRefGoogle Scholar
  148. 148.
    Mérida Rodrigo L, Faus Felipe V, Poveda Gómez F, García AJ. Agranulocytosis from metamizole: a potential problem for the British population. Rev Clin Esp. 2009;209:176–9.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Agarwal AK, Kumar M, Illyas SS. Reviewing drug package inserts available in United Arab Emirates for USFDA recommended pharmacogenomic information. J Pharm Res. 2017;2:1–4.Google Scholar
  150. 150.
    Central Bureau of statistics. Available at: http://www.cbs.gov.il/. Updated April 8, 2018. Accessed April 28, 2018.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute for Drug Research, School of Pharmacy, Faculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael
  2. 2.Tissue Typing UnitHadassah-Hebrew University Medical CenterJerusalemIsrael

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