Current status and prospects of nucleic acid mass spectrometry in clinical pharmacogenomics

Abstract

Pharmacogenomics is an essential means to achieve personalized medicine. Multi-gene and multi-loci panel testing is an inevitable trend in its development, comprehensively analyzing the impact of genes on medications from the perspective of drug metabolism, efficacy, and adverse reactions, thereby formulating individualized regimen plans. Based on the requirements for detection throughput, nucleic acid mass spectrometry with medium throughput has become a suitable platform for pharmacogenomic testing. In this review, we examine the application of this technology in clinical pharmacogenomics, discuss its current challenges, and put forward suggestions for advancing its clinical application and precision medicine.

Keywords

Nucleic acid mass spectrometry / Clinical pharmacogenomics / Precision medicine / Genetic testing / personalized medicine

Declarations

Not applicable.

Authors' contributions

Z.P.: Writing - review & editing. Yilei Li: Writing - review & editing, Funding acquisition. M.L.: Writing - original draft. L.X.: Resources. C.Y. Investigation. W.H.: Formal analysis. C.J.: Project administration. Z.C.: Writing - original draft. D.L. Project administration.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work was supported by grants from the Wu Jieping Medical Foundation (320.6750.2020-04-1), China Zhongguancun Precision Medicine Science and Technology Foundation (ZGC-YXKY-23).

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Yilei Li reports financial support was provided by Wu Jieping Medical Foundation. Yilei Li reports financial support was provided by China zhongguancun Precision Medicine science and technology foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

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Authors' other information

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References

[1] Pirmohamed Munir. Pharmacogenomics: current status and future perspectives. Nat Rev Genet. 2023 Jun;24(6):350-362.

[2] Sadee W, Wang D, Hartmann K, et al. Pharmacogenomics: driving personalized medicine. Pharmacol Rev. 2023; 75(4):789-814.

[3] Lee CR, Luzum JA, Sangkuhl K, et al. Clinical pharmacogenetics implementation consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther. 2022; 112(5):959-967.

[4] De Pieri M, Ferrari M, Marino F, et al. Functional single nucleotide polymorphisms in dopaminergic receptors D2 predict clinical response to Cariprazine. Front Pharmacol. 2023.

[5] Phillips EJ, Sukasem C, Whirl-Carrillo M, et al. Clinical pharmacogenetics implementation consortium guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 update. Clin Pharmacol Ther. 2018; 103(4):574-581.

[6] FDA. Table of Pharmacogenomic Biomarkers in Drug Labeling. http://ttps://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling.

[7] FDA. Table of Pharmacogenetic Associations. http://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations (2022).

[8] Zhou H, Chen X, Zhang W, et al. & National Health and Family Planning Commission Individualized Medicine Testing Technology Expert Committee. (2015). Technical guidelines for genetic testing of drug-metabolizing enzymes and drug targets (trial) [Electronic version]. Retrieved from http://www.improve-medical.com/Uploads/attached/file/20171207/20171207135118_57361.pdf.

[9] Zhan Q, Zeng Y, Wang J, et al. & National Health and Family Planning Commission Individualized Medicine Testing Technology Expert Committee. (2017). Technical guidelines for individualized treatment of tumors (trial) [Electronic version]. Retrieved from http://www.improve-medical.com/Uploads/attached/file/20171207/20171207141157_13839.pdf.

[10] Satam H, Joshi K, et al. Next-generation sequencing technology: current trends and advancements. Biology. 2023; 12(7):997 Jul 13.

[11] Expert China. Consensus Group on the application of nucleic acid mass spectrometry. China nucleic acid mass spectrometry application expert consensus. Natl Med J China. 2018; 98(12).

[12] Storm N, Darnhofer-Patel B. MALDI-TOF mass spectrometry-based SNP genotype. Single Nucleotide Polymorph Methods Protoc. 2003:241-262.

[13] Zhao X, Xiao D. Research progress of mass-spectrometric technique in nucleic acid detection and analysis. Chin J Lab Med. 2024; 58(1):98-106.

[14] Gao X, Tan BH, Sugrue RJ, et al. MALDI mass spectrometry for nucleic acid analysis. Top Curr Chem. 2013; 331:55-77.

[15] Ellis JA, Ong B. The MassARRAY® system for targeted SNP genotype. Genotype Methods Protoc. 2017:77-94.

[16] Spear BB, Heath-Chiozzi M, Huff J. Clinical application of pharmacogenetics. Trends Mol Med. 2001; 7:201-204.

[17] Belle DJ, Singh H. Genetic factors in drug metabolism. Am Fam Physician. 2008; 77(11):1553-1560.

[18] Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 update. Clin Pharmacol Ther. 2017; 102(3):397-404.

[19] Scott SA, Sangkuhl K, Gardner EE, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C 19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther. 2011; 90(2):328-332.

[20] Swen JJ, Nijenhuis M, de Boer A, et al. Pharmacogenetics: from bench to byte—an update of guidelines. Clin Pharmacol Ther. 2011; 89(5):662-673.

[21] Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin Pharmacol Ther. 2022; 111(5):1007-1021.

[22] Karnes JH, Rettie AE, Somogyi AA, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B genotypes and phenytoin dosing: 2020 update. Clin Pharmacol Ther. 2021; 109(2):302-309.

[23] Nijenhuis M., Manson L., Soree B., et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of CYP2C9, HLA-A and HLA-B with anti-epileptic drugs. 2023.

[24] Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017; 102(1):37.

[25] Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes and serotonin reuptake inhibitor antidepressants. Clin Pharmacol Ther. 2023; 114(1):51-68.

[26] Beunk L, Nijenhuis M, Soree B, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP3A4 and CYP1A2 and antipsychotics. Eur J Hum Genet. 2023:1-8.

[27] Relling MV, Schwab M, Whirl-Carrillo M, et al. Clinical pharmacogenetics implementation consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. Clin Pharmacol Ther. 2019; 105(5):1095-1105.

[28] Birdwell KA, Decker B, Barbarino JM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015; 98(1):19-24.

[29] Chandran V, Siannis F, Rahman P, et al. Folate pathway enzyme gene polymorphisms and the efficacy and toxicity of methotrexate in psoriatic arthritis. J Rheumatol. 2010; 37(7):1508-1512.

[30] Amstutz U, Henricks LM, Offer SM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update. Clin Pharmacol Ther. 2018; 103(2):210-216.

[31] Hulshof EC, Deenen MJ, Nijenhuis M, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan. Eur J Hum Genet. 2023; 31(9):982-987.

[32] Côté JF, Kirzin S, Kramar A, et al. UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. Clin Cancer Res. 2007; 13(11):3269-3275.

[33] A-li YE, Hai-yan ZHANG, Ya-ling DOU, et al. Establishment of MALDI TOF-MS Technique Platform for Detecting Cytochrome P450 Gene Polymorphism[J]. (Septe). J Mod Lab Med. 2016; 31(5).

[34] LIU Z, CUI K, YANG L, et al. Performance verification of a time-of-flight mass spectrometry based cardiovascular drug-related polygene detection system. Chin J Lab Med. 2020:51-57.

[35] Hall-Flavin DK, Winner JG, Allen JD, et al. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharm Genom. 2013; 23(10):535-548.

[36] Altar CA, Carhart J, Allen JD, et al. Clinical utility of combinatorial pharmacogenomics-guided antidepressant therapy: evidence from three clinical studies. Mol Neuropsychiatry. 2015; 1(3):145-155.

[37] Jinquan HE, Jun LUO, Ting CHEN, et al. Efficacy and safety analysis of pharmacogenomics-based personalized medication for treatment-resistant depression. (December). Lab Med Clin. 2023; 20(23).

[38] Jiqing Li. Evaluation of the application effect of pharmacogenomics testing for antipsychotic in real-world scenarios and research on personalized medication. Shandong University, 2023. doi:10.27272/d.cnki.gshdu.2023.000779.

[39] Kang Z, Qin Y, Sun Y, et al. Multigenetic pharmacogenomics-guided treatment vs treatment as usual among hospitalized men with Schizophrenia: a randomized clinical trial. JAMA Netw Open. 2023; 6(10) e2335518-e2335518.

[40] Zeng F, Liu Y, Ouyang Q, et al. Rs3802278 in 3’-UTR of SULF1 associated with platinum resistance and survival in Chinese epithelial ovarian cancer patients. J Chemother. 2021; 33(8):564-569.

[41] Chen J, Wu L, Wang Y, et al. Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity. Tumor Biol. 2016; 37:2275-2284.

[42] Hongxia TIAN, Xuchao ZHANG, Zhen WANG, et al. Establishment and application of a MassARRAY platform-based method to detect multiplex genetic mutations in lung cancer. Chin J Clin Oncol. 2015; 42(17).

[43] Hongmei Sun, Chao Lü, Xuan Sun, et al. Efficacy and adverse reactions of donepezil:a pharmacogenomic study. Chin J Geriatr Heart Brain Vessel Dis. Feb 2024; 6(2).

[44] Li X, Zhang J, Wu X, et al. Polymorphisms of ABAT, SCN2A and ALDH5A1 may affect valproic acid responses in the treatment of epilepsy in Chinese. Pharmacogenomics. 2016; 17(18):2007-2014.

[45] Chen J, Su Q, Qin J, et al. Correlation of MCT1 and ABCC2 gene polymorphisms with valproic acid resistance in patients with epilepsy on valproic acid monotherapy. Drug Metab Pharmacokinet. 2019; 34(3):165-171.

[46] VCBeat Research. Clinical mass spectrometry white paper: new directions of precision medicine after NGS, Seven Technologies to accelerate the localization of clinical mass spectrometry. VBDATA.CN, 2022. http://www.vbdata.cn/reportDetail?rid=aff924f2fb3972551a10b1daaf9855ec.