Actionable pharmacogenetic variants in Hong Kong Chinese exome sequencing data and projected prescription impact in the Hong Kong population


Autoři: Mullin Ho Chung Yu aff001;  Marcus Chun Yin Chan aff001;  Claudia Ching Yan Chung aff001;  Andrew Wang Tat Li aff002;  Chara Yin Wa Yip aff002;  Christopher Chun Yu Mak aff001;  Jeffrey Fong Ting Chau aff001;  Mianne Lee aff001;  Jasmine Lee Fong Fung aff001;  Mandy Ho Yin Tsang aff001;  Joshua Chun Ki Chan aff001;  Wilfred Hing Sang Wong aff001;  Jing Yang aff001;  William Chun Ming Chui aff002;  Patrick Ho Yu Chung aff003;  Wanling Yang aff001;  So Lun Lee aff004;  Godfrey Chi Fung Chan aff001;  Paul Kwong Hang Tam aff003;  Yu Lung Lau aff001;  Clara Sze Man Tang aff003;  Kit San Yeung aff001;  Brian Hon Yin Chung aff001
Působiště autorů: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China aff001;  Department of Pharmacy, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China aff002;  Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China aff003;  Department of Paediatrics and Adolescent Medicine, Duchess of Kent Children's Hospital, Pokfulam, Hong Kong SAR, China aff004;  Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China aff005;  Department of Paediatrics and Adolescent Medicine, The Hong Kong Children’s Hospital, Kowloon Bay, Hong Kong SAR, China aff006;  Dr Li Dak-Sum Research Centre, The University of Hong Kong–Karolinska Institutet Collaboration in Regenerative Medicine, Pokfulam, Hong Kong SAR, China aff007
Vyšlo v časopise: Actionable pharmacogenetic variants in Hong Kong Chinese exome sequencing data and projected prescription impact in the Hong Kong population. PLoS Genet 17(2): e1009323. doi:10.1371/journal.pgen.1009323
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009323

Souhrn

Preemptive pharmacogenetic testing has the potential to improve drug dosing by providing point-of-care patient genotype information. Nonetheless, its implementation in the Chinese population is limited by the lack of population-wide data. In this study, secondary analysis of exome sequencing data was conducted to study pharmacogenomics in 1116 Hong Kong Chinese. We aimed to identify the spectrum of actionable pharmacogenetic variants and rare, predicted deleterious variants that are potentially actionable in Hong Kong Chinese, and to estimate the proportion of dispensed drugs that may potentially benefit from genotype-guided prescription. The projected preemptive pharmacogenetic testing prescription impact was evaluated based on the patient prescription data of the public healthcare system in 2019, serving 7.5 million people. Twenty-nine actionable pharmacogenetic variants/ alleles were identified in our cohort. Nearly all (99.6%) subjects carried at least one actionable pharmacogenetic variant, whereas 93.5% of subjects harbored at least one rare deleterious pharmacogenetic variant. Based on the prescription data in 2019, 13.4% of the Hong Kong population was prescribed with drugs with pharmacogenetic clinical practice guideline recommendations. The total expenditure on actionable drugs was 33,520,000 USD, and it was estimated that 8,219,000 USD (24.5%) worth of drugs were prescribed to patients with an implicated actionable phenotype. Secondary use of exome sequencing data for pharmacogenetic analysis is feasible, and preemptive pharmacogenetic testing has the potential to support prescription decisions in the Hong Kong Chinese population.

Klíčová slova:

Alleles – Bioinformatics – Drug metabolism – Glucose-6-phosphate dehydrogenase deficiency – Hong Kong – Chinese people – Pharmacogenetics – Variant genotypes


Zdroje

1. International Conference on Harmonisation; Guidance on E15 Pharmacogenomics Definitions and Sample Coding; Availability. Notice. Fed Regist. 2008;73(68):19074–6. Epub 2008/08/06. 18677821.

2. Doble B, Schofield DJ, Roscioli T, Mattick JS. Prioritising the application of genomic medicine. NPJ Genom Med. 2017;2:35. Epub 2017/12/22. doi: 10.1038/s41525-017-0037-0 29263844; PubMed Central PMCID: PMC5698310.

3. Roden DM, Van Driest SL, Mosley JD, Wells QS, Robinson JR, Denny JC, et al. Benefit of Preemptive Pharmacogenetic Information on Clinical Outcome. Clin Pharmacol Ther. 2018;103(5):787–94. Epub 2018/01/30. doi: 10.1002/cpt.1035 29377064; PubMed Central PMCID: PMC6134843.

4. Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharmacol Ther. 2011;89(3):464–7. Epub 2011/01/29. doi: 10.1038/clpt.2010.279 21270786; PubMed Central PMCID: PMC3098762.

5. Barbarino JM, Whirl-Carrillo M, Altman RB, Klein TE. PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018;10(4):e1417. Epub 2018/02/24. doi: 10.1002/wsbm.1417 29474005; PubMed Central PMCID: PMC6002921.

6. McDonagh EM, Whirl-Carrillo M, Garten Y, Altman RB, Klein TE. From pharmacogenomic knowledge acquisition to clinical applications: the PharmGKB as a clinical pharmacogenomic biomarker resource. Biomark Med. 2011;5(6):795–806. Epub 2011/11/23. doi: 10.2217/bmm.11.94 22103613; PubMed Central PMCID: PMC3339046.

7. Bush WS, Crosslin DR, Owusu-Obeng A, Wallace J, Almoguera B, Basford MA, et al. Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network. Clin Pharmacol Ther. 2016;100(2):160–9. Epub 2016/02/10. doi: 10.1002/cpt.350 26857349; PubMed Central PMCID: PMC5010878.

8. Wright GEB, Carleton B, Hayden MR, Ross CJD. The global spectrum of protein-coding pharmacogenomic diversity. Pharmacogenomics J. 2018;18(1):187–95. Epub 2016/10/26. doi: 10.1038/tpj.2016.77 27779249; PubMed Central PMCID: PMC5817389.

9. Gordon AS, Tabor HK, Johnson AD, Snively BM, Assimes TL, Auer PL, et al. Quantifying rare, deleterious variation in 12 human cytochrome P450 drug-metabolism genes in a large-scale exome dataset. Hum Mol Genet. 2014;23(8):1957–63. Epub 2013/11/28. doi: 10.1093/hmg/ddt588 24282029; PubMed Central PMCID: PMC3959810.

10. Fujikura K, Ingelman-Sundberg M, Lauschke VM. Genetic variation in the human cytochrome P450 supergene family. Pharmacogenet Genomics. 2015;25(12):584–94. Epub 2015/09/05. doi: 10.1097/FPC.0000000000000172 26340336.

11. Ingelman-Sundberg M, Mkrtchian S, Zhou Y, Lauschke VM. Integrating rare genetic variants into pharmacogenetic drug response predictions. Hum Genomics. 2018;12(1):26. Epub 2018/05/26. doi: 10.1186/s40246-018-0157-3 29793534; PubMed Central PMCID: PMC5968569.

12. Zhou Y, Ingelman-Sundberg M, Lauschke VM. Worldwide Distribution of Cytochrome P450 Alleles: A Meta-analysis of Population-scale Sequencing Projects. Clin Pharmacol Ther. 2017;102(4):688–700. Epub 2017/04/06. doi: 10.1002/cpt.690 28378927; PubMed Central PMCID: PMC5600063.

13. Qin W, Du Z, Xiao J, Duan H, Shu Q, Li H. Evaluation of clinical impact of pharmacogenomics knowledge involved in CPIC guidelines on Chinese pediatric patients. Pharmacogenomics. 2020;21(3):209–19. Epub 2020/01/23. doi: 10.2217/pgs-2019-0153 31967514.

14. Kawaguchi S, Higasa K, Shimizu M, Yamada R, Matsuda F. HLA-HD: An accurate HLA typing algorithm for next-generation sequencing data. Hum Mutat. 2017;38(7):788–97. Epub 2017/04/19. doi: 10.1002/humu.23230 28419628.

15. Poplin R, Ruano-Rubio V, DePristo MA, Fennell TJ, Carneiro MO, Van der Auwera GA, et al. Scaling accurate genetic variant discovery to tens of thousands of samples. bioRxiv. 2018:201178. doi: 10.1101/201178

16. Yang H, Wang K. Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR. Nat Protoc. 2015;10(10):1556–66. Epub 2015/09/18. doi: 10.1038/nprot.2015.105 26379229; PubMed Central PMCID: PMC4718734.

17. Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2019;47(D1):D886–d94. Epub 2018/10/30. doi: 10.1093/nar/gky1016 30371827; PubMed Central PMCID: PMC6323892.

18. Ioannidis NM, Rothstein JH, Pejaver V, Middha S, McDonnell SK, Baheti S, et al. REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants. Am J Hum Genet. 2016;99(4):877–85. Epub 2016/09/27. doi: 10.1016/j.ajhg.2016.08.016 27666373; PubMed Central PMCID: PMC5065685.

19. Zhou Y, Mkrtchian S, Kumondai M, Hiratsuka M, Lauschke VM. An optimized prediction framework to assess the functional impact of pharmacogenetic variants. Pharmacogenomics J. 2019;19(2):115–26. Epub 2018/09/13. doi: 10.1038/s41397-018-0044-2 30206299; PubMed Central PMCID: PMC6462826 that they have no conflict of interest.

20. Karczewski K. LOFTEE (Loss-Of-Function Transcript Effect Estimator) [cited 2019 4 April]. Available from: https://github.com/konradjk/loftee.

21. Gaedigk A, Sangkuhl K, Whirl-Carrillo M, Twist GP, Klein TE, Miller NA. The Evolution of PharmVar. Clin Pharmacol Ther. 2019;105(1):29–32. Epub 2018/12/12. doi: 10.1002/cpt.1275 30536702; PubMed Central PMCID: PMC6312487.

22. Zhang X, Yin JF, Zhang J, Kong SJ, Zhang HY, Chen XM. UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis. Cancer Chemother Pharmacol. 2017;80(1):135–49. Epub 2017/06/07. doi: 10.1007/s00280-017-3344-3 28585035.

23. SK M. Recent perspectives in glucose-6-phosphate dehydrogenase (G6PD) deficiency. Topical Update—The Hong Kong College of Pathologists 2007 [cited 2020 23 January]. Available from: http://www.hkcpath.org/article/recent-perspectives-glucose-6-phosphate-dehydrogenase-g6pd-deficiency.

24. Census and Statistics Department TGotHKSAR. Women and men in Hong Kong—Key statistics, 2019 Edition 2019 [cited 2020 23 January]. Available from: https://www.censtatd.gov.hk/hkstat/sub/sp180.jsp?productCode=B1130303.

25. Hong Kong Hospital Authority. Hospital authority statistical report 2015–2016 2016 [cited 2020 24 March]. Available from: https://www3.ha.org.hk/data/HAStatistics/StatisticalReport/.

26. Hospital Authority. Hospital Authority Annual Report 2018–2019 [cited 2020 24 March]. Available from: https://www.legco.gov.hk/yr19-20/chinese/counmtg/papers/cm20191218-sp077-ec.pdf

27. Chan W, Li MS, Sundaram SK, Tomlinson B, Cheung PY, Tzang CH. CYP2D6 allele frequencies, copy number variants, and tandems in the population of Hong Kong. J Clin Lab Anal. 2019;33(1):e22634. Epub 2018/08/03. doi: 10.1002/jcla.22634 30069923; PubMed Central PMCID: PMC6430334.

28. Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA, Zhao X, et al. NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nat Genet. 2016;48(4):367–73. Epub 2016/02/16. doi: 10.1038/ng.3508 26878724; PubMed Central PMCID: PMC5029084.

29. Ford LT, Berg JD. Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come. J Clin Pathol. 2010;63(4):288–95. Epub 2010/04/01. doi: 10.1136/jcp.2009.069252 20354201.

30. Chanfreau-Coffinier C, Hull LE, Lynch JA, DuVall SL, Damrauer SM, Cunningham FE, et al. Projected Prevalence of Actionable Pharmacogenetic Variants and Level A Drugs Prescribed Among US Veterans Health Administration Pharmacy Users. JAMA Netw Open. 2019;2(6):e195345. Epub 2019/06/08. doi: 10.1001/jamanetworkopen.2019.5345 31173123; PubMed Central PMCID: PMC6563578.

31. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, et al. SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med. 2008;359(8):789–99. Epub 2008/07/25. doi: 10.1056/NEJMoa0801936 18650507.

32. Min S, Papaz T, Lafreniere-Roula M, Nalli N, Grasemann H, Schwartz SM, et al. A randomized clinical trial of age and genotype-guided tacrolimus dosing after pediatric solid organ transplantation. Pediatr Transplant. 2018;22(7):e13285. Epub 2018/09/05. doi: 10.1111/petr.13285 30178515.

33. Matreyek KA, Starita LM, Stephany JJ, Martin B, Chiasson MA, Gray VE, et al. Multiplex assessment of protein variant abundance by massively parallel sequencing. Nat Genet. 2018;50(6):874–82. Epub 2018/05/23. doi: 10.1038/s41588-018-0122-z 29785012; PubMed Central PMCID: PMC5980760.

34. Kwok J, Guo M, Yang W, Lee CK, Ho J, Tang WH, et al. HLA-A, -B, -C, and -DRB1 genotyping and haplotype frequencies for a Hong Kong Chinese population of 7595 individuals. Hum Immunol. 2016;77(12):1111–2. Epub 2016/10/25. doi: 10.1016/j.humimm.2016.10.005 27769748.

35. Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot JS, Johnson JA, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther. 2011;90(2):328–32. Epub 2011/07/01. doi: 10.1038/clpt.2011.132 21716271; PubMed Central PMCID: PMC3234301.

36. Walker GJ, Harrison JW, Heap GA, Voskuil MD, Andersen V, Anderson CA, et al. Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease. Jama. 2019;321(8):773–85. Epub 2019/02/27. doi: 10.1001/jama.2019.0709 30806694; PubMed Central PMCID: PMC6439872.

37. He Y, Li J, Mao W, Zhang D, Liu M, Shan X, et al. HLA common and well-documented alleles in China. Hla. 2018;92(4):199–205. Epub 2018/08/04. doi: 10.1111/tan.13358 30073798.


Článek vyšel v časopise

PLOS Genetics


2021 Číslo 2
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Hypertenze a hypercholesterolémie – synergický efekt léčby
nový kurz
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Úloha kombinovaných preparátů v léčbě arteriální hypertenze
Autoři: prof. MUDr. Martin Haluzík, DrSc.

Halitóza
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Terapie roztroušené sklerózy v kostce
Autoři: MUDr. Dominika Šťastná, Ph.D.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se