Objective  To analyze the research status of immunosuppressive pharmacogenomics.

Methods  The Web of Science database was searched for relevant references on immunosuppressive pharmacogenomics studies from Janurary 2012 to Febrary 2022, and the search results were ana-lyzed using bibliometric methods and CiteSpace visualization software.

Results  Totally 1 062 refer-ences were retrieved from the Web of Science database. The number of annual releases continued to increase, and the cumulative number of releases grew steadily. The United States had the largest share of 27.8% of the total number of published documents, followed by China with 15.6%. As the countries that publish the most papers, the U.S. and China have not yet formed a relatively close cooperation network. China’s scientific research cooperation with other countries is not close enough and relatively independent. Harvard Medical School is a leading research institution in this field. Academic collab-oration circles focus on geographically close areas. Cross-regional cooperation is relatively weak, and extensive cooperative relationships and academic communities have not yet been formed. The top 10 authors are roughly divided into two research groups, with Van Gelder Teun, Hesselink Dennis, and Israni Ajay as the core authors. Studies have focused on the impact of pharmacogenomic differences in calcineurin inhibitors such as tacrolimus on individual metabolism. The immunosuppressants studied mainly play a role in transplantation, inflammatory bowel disease, glomerulonephritis, and other fields.

Conclusion  Genomic research on immunosuppressive drugs is still on the rise, with the United States leading the way; China is second, at the forefront of research, and relatively independent. The effect of pharmacogenomics on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors is still a relatively mature research direction in the field of solid organ transplantation.

1.Parlakpinar H, Gunata M.Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs[J]. Immunopharmacol Immunotoxicol, 2022, 43(6): 651-665. DOI: 10.1080/ 08923973.2021.1966033.

2.Lee HJ, Li CW, Hammerstad SS, et al. Immunogenetics of autoimmune thyroid diseases: a comprehen-sive review[J]. J Autoimmun, 2015, 64: 82-90. DOI: 10.1016/j.jaut.2015.07.009.

3.袁梅, 闫美玲, 张弋.活化T细胞核因子调控基因在钙调磷酸酶抑制剂药效学监测中的研究进展[J]. 实用器官移植电子杂志, 2015, 3(3): 172-177. [Yuan M, Yan ML, Zhang Y.Research progress of activated T nuclear factor regulatory gene in pharmacodynamic monitoring of calcineurin inhibitors[J]. Practical Journal of Organ Transplantation (Electronic Version), 2015, 3(3): 172-177.] DOI: 10.3969/j.issn.2095-5332.2015.03.016.

4.Baraldo M.Meltdose tacrolimus pharmacokinetics[J]. Transplant Proc, 2016，48(2): 420-423. DOI: 10.1016/j.transproceed.2016.02.002.

5.Singh S, Allegretti JR, Siddique SM, et al. AGA technical review on the management of moderate to severe ulcerative colitis[J]. Gastroenterology, 2020, 158(5): 1465-1496 e1417. DOI: 10.1053/j.gastro.2020.01.007.

6.胡祎明. 临床特殊治疗药物霉酚酸、他克莫司及万古霉素浓度监测的研究现状与进展[J]. 检验医学与临床, 2020, 17(12): 1767-1771. [Hu WM. Research status and progress of concentration monitoring of mycophe-nolic acid, tacrolimus and vancomycin[J]. Laboratory Medicine and Clinic, 2020, 17(12): 1767-1771.] DOI: 10.3969/j.issn.1672-9455.2020.12.042.

7.谢秋芬, 种姗, 胡琨, 等.国内外药物基因组学相关指南的现状[J]. 中国临床药理学杂志, 2022, 38(16): 1954-1957. [Xie QF, Chong S, Hu K, et al. Current status of pharmacogenomic guidelines in the domestic and overseas[J]. Chinese Journal of Clinical Pharmacology, 2022, 38(16): 1954-1957.] DOI: 10.13699/j.cnki.1001- 6821.2022.16.025.

8.吴云, 王家莹, 卢映蓉, 等. 器官移植患者他克莫司血药浓度影响因素的研究进展[J]. 医药导报, 2022, 41(5): 669-674. [Wu Y, Wang JY, Lu YR, et al. Research progress on influencing factors of tacrolimus concen-tration in patients undergoing organ transplant[J]. Herald of Medicine, 2022, 41(5): 669-674.] DOI: 10.3870/j.issn.1004-0781.2022.05.013.

9.Medeiros M, Castaneda-Hernandez G, Ross CJ, et al. Use of pharmacogenomics in pediatric renal transplant recipients[J]. Front Genet, 2015, 6: 41. DOI: 10.3389/fgene.2015.00041.

10.Kim T, Han N, Sohn M, et al. Pharmacogenomic biomarker information in FDA-approved paediatric drug labels[J]. Basic Clin Pharmacol Toxicol, 2015, 116(5): 438-444.DOI: 10.1111/bcpt.12341.

11.Swen JJ, Nijenhuis M, de Boer A,  et al. Pharmacogenetics: from bench to byte--an update of guide-lines[J]. Clin Pharmacol Ther, 2011, 89(5): 662-673. DOI: 10.1038/clpt.2011.34.

12.Overby CL, Tarczy-Hornoch P, Hoath JI, et al. Feasibility of incorporating genomic knowledge into electronic medical records for pharmacogenomic clinical decision support[J]. BMC Bioinformatics, 2010, 11(Suppl 9): S10.DOI: 10.1186/1471-2105-11-S9-S10.

13.Birdwell KA, Grady B, Choi L, et al. The use of a DNA biobank linked to electronic medical records to characterize pharmacogenomic predictors of tacrolimus dose requirement in kidney transplant recip-ients[J]. Pharmacogenet Genomics, 2012, 22(1): 32-42. DOI: 10.1097/FPC.0b013e32834e1641.

14.熊滨, 罗绍清.文献计量学的应用及其缺陷[J]. 南昌大学学报(人文社会科学版), 2005, 36(1): 158-160. [Xiong B, Luo SQ.Bibliometrical application and its limitation as a new means of exterior history research[J]. Journal of Nanchang University (Humanities and Social Sciences Edition), 2005, 36(1): 158-160.] DOI: 10.3969/j.issn.1006-0448.2005.01.032.

15.许培扬, 余嘉, 莫妮, 等.医学文献计量分析研究进展[J]. 医学情报工作, 2000, 21(5): 7-11. [Xu PY, Yu J, Mo N, et al. Re-search progress in metrological analysis of medical literature[J]. Journal of Medical Intelligence, 2000, 21(5): 7-11.] DOI: 10.3969/j.issn.1673-6036.2000.05.004.

16.郭奕彤, 谭志刚. 肾移植与免疫抑制剂的应用研究: SCI数据库2001/2010年收录文献检索分析[J]. 中国组织工程研究, 2012, 16(5): 885-894. [Guo YT, Tan ZG. Immunosuppressant medicines for renal transplantation: a literature analysis based on Science Citation Index database from 2001 to 2010[J]. Chinese Journal of Tissue Engineering Research, 2012, 16(5): 885-894.] DOI: 10.3969/j.issn.1673-8225.2012.05.030.

17.Weinshilboum RM, Sladek SL.Mercaptopurine pharmacogenetics: monogenic inheritance of erythro-cyte thiopurine methyltransferase activity[J]. Am J Hum Genet, 1980, 32(5): 651-662. https://pubmed.ncbi.nlm.nih.gov/7191632/.

18.Staatz CE, Goodman LK, Tett SE.Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: PartⅡ[J]. Clin Pharmacokinet, 2010, 49(4): 207-221. DOI: 10.2165/11317550-000000000-00000.

19.Birdwell KA, Decker B, Barbarino JM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing[J]. Clin Pharmacol Ther, 2015, 98(1): 19-24. DOI: 10.1002/cpt.113.

20.Hesselink DA, Bouamar R, Elens L, et al. The role of pharmacogenetics in the disposition of and re-sponse to tacrolimus in solid organ transplantation[J]. Clin Pharmacokinet, 2014, 53(2): 123-139. DOI: 10.1007/s40262-013-0120-3.

21.Thervet E, Loriot MA, Barbier S, et al. Optimization of initial tacrolimus dose using pharmacogenetic testing[J]. Clin Pharmacol Ther, 2010, 87(6): 721-726. DOI: 10.1038/clpt.2010.17.

22.Shuker N, Bouamar R, van Schaik RH, et al. A randomized controlled trial comparing the efficacy of CYP3A5 genotype-based with body-weight-based tacrolimus dosing after living donor kidney trans-plantation[J]. Am J Transplant, 2016, 16(7): 2085-2096. DOI: 10.1111/ajt.13691.

23.Elens L, Bouamar R, Hesselink DA, et al. A new functional CYP3A4 intron 6 polymorphism significantly affects tacrolimus pharmacokinetics in kidney transplant recipients[J]. Clin Chem, 2011, 57(11): 1574-1583. DOI: 10.1373/clinchem.2011.165613.

24.Brunet M, van Gelder T, Asberg A, et al. Therapeutic drug monitoring of tacrolimus-personalized therapy: second consensus report[J]. Ther Drug Monit, 2019, 41(3): 261-307. DOI: 10.1097/FTD.0000000000000640.

25.Sadowski CE, Lovric S, Ashraf S, et al. A single-gene cause in 29.5% of cases of steroid-resistant ne-phrotic syndrome[J]. J Am Soc Nephrol, 2015, 26(6): 1279-1289.DOI: 10.1681/ASN.2014050489.

26.Rojas L, Neumann I,  Herrero MJ, et al.Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies[J]. Pharmacogenomics J, 2015, 15(1): 38-48. DOI: 10.1038/tpj.2014.38.