MALDI-TOF MS-based SNP assay used to determine the appropriate antidepression for Chinese patients

Abstract

Medicine remains the preferred primary treatment for depression, although some patients show remarkable individual variations in achieving satisfactory clinical outcomes during medication. Genetic polymorphisms cause approximately 40 % of individual differences in treatment response. Therefore, this study aimed to develop a technique to identify single nucleotide polymorphisms (SNPs) associated with the metabolism, effectiveness, and side effects of antidepressant medications in Chinese patients. Bibliometrics was used to search literature related to “depression” and “SNP” in Web of Science. The obtained SNP information was screened using the PharmGKB database. By designing and optimizing primers and conducting a compound amplification system, a method was established based on MALDI-TOF MS to detect polymorphisms associated with the antidepressant drugs, including sertraline, fluoxetine, citalopram, escitalopram, venlafaxine, fluvoxamine, paroxetine, and mirtazapine. The accuracy and sensitivity of the established method were verified by Sanger sequencing. A total of 10,043 articles were screened from the database, and 46 SNPs with a mutation frequency of >1 % in Asian populations and annotated with relevant clinical drugs were extracted from the PharmGKB database. This method was compared with the results of Sanger sequencing, and the accuracy of the detection results was 100 %. The MALDI-TOF MS-based SNP assay developed in this study can be a fast, convenient and effective way for patients to find the right medication for themselves. Moreover, we found that this SNP assay holds the promise of being a potential reference tool for assessing individualised differences in drug efficacy, not only for screening the causes of poor antidepressant efficacy in patients after taking medication, but also for advising physicians to understand individualised differences in drug efficacy.