Pharmacogenomics最新文献_第4页

Pharmacogenomics and response to lithium in bipolar disorder.

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-02-25 DOI: 10.1080/14622416.2025.2470605

Pasquale Paribello, Ulker Isayeva, Claudia Pisanu, Alessio Squassina, Mirko Manchia

{"title":"Pharmacogenomics and response to lithium in bipolar disorder.","authors":"Pasquale Paribello, Ulker Isayeva, Claudia Pisanu, Alessio Squassina, Mirko Manchia","doi":"10.1080/14622416.2025.2470605","DOIUrl":"10.1080/14622416.2025.2470605","url":null,"abstract":"Aims: The present review explores the existing evidence on pharmacogenomic tests for prediction of lithium response in the treatment of bipolar disorder. We focused our research article on reports describing findings from genome-wide association studies, polygenic risk scores, and gene expression analyses associated with lithium response.Methods: We conducted a non-systematic review of studies from PubMed/Medline by using terms such as \"pharmacogenomics,\" \"GWAS,\" \"gene expression,\" and \"lithium response.\" Inclusion criteria focused on original research involving human subjects and assessing lithium response outcomes as well as in vitro studies. An extensive pearl-growing strategy was employed to further enlarge the scope of the piece by capitalizing on the knowledge of study authors on the subject.Results: The observed results, albeit promising, remain preliminary in terms of clinical relevance. Machine learning combining genetic and clinical data appears associated with moderate success in predicting lithium responsiveness. Gene expression studies and genome-wide association studies have helped identify possible targets of lithium and have the potential to support target-specific drug research.Conclusions: Pharmacogenomics may support further discoveries in precision medicine further enlarging our understanding of the underlying mechanisms of lithium for its efficacy. However, clinical applications currently appear out of reach in the near future.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"689-706"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Posttransplantation diabetes mellitus (PTDM): pharmacological aspects and genetic predispositions.

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-02-28 DOI: 10.1080/14622416.2025.2470613

Dorian Chastagner, Hélène Arnion, Clément Danthu, Fatouma Touré, Nicolas Picard

{"title":"Posttransplantation diabetes mellitus (PTDM): pharmacological aspects and genetic predispositions.","authors":"Dorian Chastagner, Hélène Arnion, Clément Danthu, Fatouma Touré, Nicolas Picard","doi":"10.1080/14622416.2025.2470613","DOIUrl":"10.1080/14622416.2025.2470613","url":null,"abstract":"Posttransplantation diabetes mellitus (PTDM) is a form of diabetes developed after solid organ or stem cell transplantation. This condition shares physiopathological traits with type 2 diabetes, including insulin resistance and β-cells dysfunction and its prevalence varies significantly based on the diagnostic criteria used. Immunosuppressive drugs directly contribute to PTDM risk through intricate impacts on glucose regulation, insulin secretion, and inflammation. In addition, modifiable and non-modifiable environmental risk factors are associated with the onset of this condition. This review aims to provide a comprehensive overview of the multifactorial nature of PTDM in order to highlight candidate genes and variants for pharmacogenetic research. An extensive literature search was conducted to identify studies on pharmacological and genetic factors influencing PTDM development. This review stresses the importance of understanding these interactions for improving PTDM management and underscores the need for further research to refine preventive approaches, ultimately enhancing patient outcomes post-transplantation.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"707-718"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer? CYP2D6基因型是否影响羟考酮剂量、药代动力学、疼痛和癌症的不良反应？

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-12-04 DOI: 10.1080/14622416.2024.2430161

Aaron K Wong, Sara Vogrin, Pal Klepstad, Justin Rubio, Brian Le, Jennifer Philip, Andrew A Somogyi

{"title":"Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer?","authors":"Aaron K Wong, Sara Vogrin, Pal Klepstad, Justin Rubio, Brian Le, Jennifer Philip, Andrew A Somogyi","doi":"10.1080/14622416.2024.2430161","DOIUrl":"10.1080/14622416.2024.2430161","url":null,"abstract":"Aims: To examine the associations between CYP2D6 and CYP3A4 polymorphisms, plasma oxycodone and metabolite concentrations, and oxycodone response (dose, pain scores, and adverse effects) in people with pain from advanced cancer.Patients & methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects), and blood (pharmacokinetics, DNA). Negative binomial regression and logistic regression were used.Results: Within 33 participants, there were no differences in oxycodone response between CYP2D6 intermediate/poor metabolisers compared to normal metabolisers.Higher plasma noroxycodone and noroxycodone/oxycodone concentration ratios had higher odds of uncontrolled average pain (OR 2.44 (95%CI 1.00-5.95), p = 0.05 and OR 10.48 (95%CI 1.42-77.15), p = 0.02, respectively).Conclusions: There was no observed benefit in CYP2D6 genotyping in oxycodone response, however monitoring noroxycodone and oxymorphone concentrations warrant further examination.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"579-586"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacogenomics in Sri Lanka: a comprehensive systematic review of the research landscape and clinical implications. 斯里兰卡的药物基因组学：对研究现状和临床影响的全面系统回顾。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-11-14 DOI: 10.1080/14622416.2024.2421743

Priyanga Ranasinghe, Hajanthy Jeyapragasam, Sandamini Liyanage, Nirmala Sirisena, Vajira Hw Dissanayake

{"title":"Pharmacogenomics in Sri Lanka: a comprehensive systematic review of the research landscape and clinical implications.","authors":"Priyanga Ranasinghe, Hajanthy Jeyapragasam, Sandamini Liyanage, Nirmala Sirisena, Vajira Hw Dissanayake","doi":"10.1080/14622416.2024.2421743","DOIUrl":"10.1080/14622416.2024.2421743","url":null,"abstract":"Aim: Pharmacogenomics is emerging in South Asia, including Sri Lanka, with potential to optimize drug therapy and reduce adverse effects. This review evaluates the state of pharmacogenomics research in Sri Lanka, emphasizing population-specific factors to guide future advancements.Materials & methods: A literature search was performed across PubMed/Web-of-Science/SciVerse-Scopus/Embase, and Sri Lanka Journals Online, along with searches for relevant theses in local health repositories/university databases. Studies were categorized into clinical correlational, descriptive or novel assay development studies.Results: Eleven published articles and eight theses were included. One study examined somatic variants (KRAS gene), while all others focused on germline variants. There were two clinical correlational studies: tamoxifen adverse effects and CYP2D6 variants and FTO gene rs9939609 variants and weight gain caused by second-generation antipsychotics. Eight descriptive studies evaluated prevalence of CYP2D6 variants, HLA-B*15:02 allele, KRAS gene mutations and variants related to statin, warfarin and anticancer drug metabolism. Additionally, nine studies developed, validated and tested novel assays for detecting key pharmacogenomically important variants.Conclusion: While pharmacogenomics research in Sri Lanka has made strides, more clinical studies and broader genomic research are needed. Overcoming challenges related to funding, public awareness and regional collaboration is essential to advance personalized medicine and improve therapeutic outcomes in Sri Lanka and South Asia.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"551-567"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between CYP3A4, CYP3A5 and ABCB1 genotype and tacrolimus treatment outcomes among allogeneic HSCT patients. 异基因造血干细胞移植患者的 CYP3A4、CYP3A5 和 ABCB1 基因型与他克莫司治疗效果之间的关系。

IF 2.1 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.2217/pgs-2023-0204

Teresa T Ho, Janelle B Perkins, Rebecca Gonzalez, James Kevin Hicks, Ronald Alvarez Martinez, Katie Duranceau, Brianna North, Jongphil Kim, Jamie K Teer, Jiqiang Yao, Sean J Yoder, Taiga Nishihori, Nelli Bejanyan, Joseph Pidala, Hany Elmariah

{"title":"Association between CYP3A4, CYP3A5 and ABCB1 genotype and tacrolimus treatment outcomes among allogeneic HSCT patients.","authors":"Teresa T Ho, Janelle B Perkins, Rebecca Gonzalez, James Kevin Hicks, Ronald Alvarez Martinez, Katie Duranceau, Brianna North, Jongphil Kim, Jamie K Teer, Jiqiang Yao, Sean J Yoder, Taiga Nishihori, Nelli Bejanyan, Joseph Pidala, Hany Elmariah","doi":"10.2217/pgs-2023-0204","DOIUrl":"10.2217/pgs-2023-0204","url":null,"abstract":"Aim: Successful treatment with tacrolimus to prevent graft versus host disease (GVHD) and minimize tacrolimus-related toxicities among allogeneic hematopoietic cell transplantation (alloHCT) recipients is contingent upon quickly achieving and maintaining concentrations within a narrow therapeutic range. The primary objective was to investigate associations between CYP3A4, CYP3A5 or ABCB1 genotype and the proportion of patients that attained an initial tacrolimus goal concentration following initiation of intravenous (iv.) and conversion to oral administration. Materials & methods: We retrospectively evaluated 86 patients who underwent HLA-matched (8/8) related donor alloHCT and were prescribed a tacrolimus-based regimen for GVHD prophylaxis. Results & conclusion: The findings of the present study suggests that CYP3A5 genotype may impact attainment of initial therapeutic tacrolimus concentrations with oral administration in alloHCT recipients.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"29-40"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing the utility of measurement methods applied in economic evaluations of pharmacogenomics applications. 评估药物基因组学应用经济评估中采用的测量方法的实用性。

IF 2.1 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-01-30 DOI: 10.2217/pgs-2023-0221

Vasileios Fragoulakis, Margarita-Ioanna Koufaki, Korina Tzerefou, Konstantinos Koufou, George P Patrinos, Christina Mitropoulou

引用次数: 0

A systematic review of single nucleotide polymorphisms affecting allopurinol pharmacokinetics and serum uric acid level. 影响别嘌醇药代动力学和血清尿酸水平的单核苷酸多态性系统综述。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-09-30 DOI: 10.1080/14622416.2024.2403969

Farah Aida A Zairol Azwan, Yi Ying Teo, Nor Asyikin Mohd Tahir, Shamin Mohd Saffian, Mohd Makmor-Bakry, Mohd Shahrir Mohamed Said

{"title":"A systematic review of single nucleotide polymorphisms affecting allopurinol pharmacokinetics and serum uric acid level.","authors":"Farah Aida A Zairol Azwan, Yi Ying Teo, Nor Asyikin Mohd Tahir, Shamin Mohd Saffian, Mohd Makmor-Bakry, Mohd Shahrir Mohamed Said","doi":"10.1080/14622416.2024.2403969","DOIUrl":"10.1080/14622416.2024.2403969","url":null,"abstract":"Aim: To summarize the effects of single nucleotide polymorphisms (SNPs) on the pharmacokinetics of allopurinol to control uric acid levels.Methods: A comprehensive search was conducted in PubMed, Web of Science and Scopus databases from inception to January 2024, includes 17 articles focusing on SNPs and pharmacokinetics of allopurinol and oxypurinol.Results: A total of 11 SNPs showed a significant association with pharmacokinetics of allopurinol and oxypurinol, as well as their potential clinical implications.Conclusion: SNPs in ATP-binding cassette super-family G member 2 (ABCG2), solute carrier family 2 member 9 (SLC2A9), solute carrier family 17 member 1 (SLC17A1), solute carrier family 22 member 12 (SLC22A12), solute carrier family 22 member 13 (SLC22A13) and PDZ domain containing 1 (PDZK1) genes were associated with allopurinol clearance, while SNPs in aldehyde oxidase 1 (AOX1) genes involved in metabolism of allopurinol. SNPs in gremlin 2, DAN family BMP antagonist (GREM2) gene impacted uric acid control, but the specific mechanism governing the expression of GREM2 remains unknown. Our study indicated that the identified SNPs show contradictory effects, reflecting inconsistencies and differences observed across various studies.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"479-494"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TPMT and NUDT15 genotyping, TPMT enzyme activity and metabolite determination for thiopurines therapy: a reference laboratory experience.

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-02-16 DOI: 10.1080/14622416.2025.2463866

Sherin Shaaban, Brandon S Walker, Yuan Ji, Kamisha Johnson-Davis

{"title":"TPMT and NUDT15 genotyping, TPMT enzyme activity and metabolite determination for thiopurines therapy: a reference laboratory experience.","authors":"Sherin Shaaban, Brandon S Walker, Yuan Ji, Kamisha Johnson-Davis","doi":"10.1080/14622416.2025.2463866","DOIUrl":"10.1080/14622416.2025.2463866","url":null,"abstract":"Aim: To share the experience of a US national reference laboratory, offering genotyping for TPMT and NUDT15, TPMT enzyme phenotyping and detection of thiopurine metabolites.Methods: Retrospective review of archived datasets related to thiopurines drug therapy including patients' data that underwent TPMT and NUDT15 genotyping, and smaller data sets where genotyping was performed with TPMT enzyme levels (phenotyping) +/- therapeutic drug monitoring (TDM).Results: Thirteen percent of patients had variants in one or both genes tested. Testing for NUDT15 revealed 3.9% additional patients requiring thiopurines dosing recommendations. A correlation between TPMT enzyme activity and TPMT polymorphisms (odds ratio OD = 71.41, p-value <0.001) and between older age and higher enzyme levels (OD = 0.98, p-value = 0.002) was identified. No correlation between sex and TPMT enzyme levels, nor between TPMT genotyping and the level of thiopurine metabolites was found.Conclusion: Adding NUDT15 to TPMT genotyping, identified additional 3.9% patients to benefit from thiopurine dose modifications. A significant correlation between genetic variants in TPMT and TPMT enzyme levels and between age and enzyme levels was established, while no correlation was identified between sex and enzyme levels nor between TPMT variation and thiopurine metabolites. Providers rely more significantly on genotyping only approach, rather than genotyping and phenotyping.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"679-688"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing the clinical utility of pharmacogenomic genotyping and next generation sequencing in a military health system adult medicine clinic. 比较药物基因组基因分型和新一代测序在军事卫生系统成人医学诊所中的临床应用。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-02-21 DOI: 10.1080/14622416.2025.2466413

David Saunders, Lydia D Hellwig, Austin Pagani, Mauricio De Castro, Mark Haigney, Lucas Poon, Nate Ehat, Andrew Heroy, Joya Libbus, Keiko Fox, Sachi Kalra, Thomas B Arnold, Clesson Turner, John Logan Black, Steven E Scherer, Ann M Moyer

{"title":"Comparing the clinical utility of pharmacogenomic genotyping and next generation sequencing in a military health system adult medicine clinic.","authors":"David Saunders, Lydia D Hellwig, Austin Pagani, Mauricio De Castro, Mark Haigney, Lucas Poon, Nate Ehat, Andrew Heroy, Joya Libbus, Keiko Fox, Sachi Kalra, Thomas B Arnold, Clesson Turner, John Logan Black, Steven E Scherer, Ann M Moyer","doi":"10.1080/14622416.2025.2466413","DOIUrl":"10.1080/14622416.2025.2466413","url":null,"abstract":"Introduction: Pharmacogenetic (PGx) screening is intended to optimize drug efficacy and reduce adverse drug reactions. Current screening options include genotyping assays for preselected PGx variants and broader next-generation sequencing panels (NGS). Few studies have directly compared preemptive PGx screening methods.Materials and methods: The two PGx methods were compared in a cross-sectional study of adult Military Health System (MHS) clinic beneficiaries. Participants had initial targeted CYP2C19/CYP2D6 genotyping at a Military Health System Laboratory. Genotyping was followed by multi-gene NGS testing. Current prescriptions were recorded and potential drug-drug interactions screened to evaluate prescribing risk.Results: All participants (100%) had at least one clinically actionable NGS panel result compared to 81% with targeted CYP2C19/CYP2D6 genotyping. Participants (n = 162) had an average of 6.6 (range 0-22) prescriptions and 2.7 (range 0-24) drug-drug interactions. Among those with at least one clinically actionable NGS result, 42% were currently taking medication with actionable CPIC guidelines (Level A/B), compared with 24% with CYP2C19/CYP2D6 genotyping. Sixteen participants (10%) had uncertain NGS panel results, with none for CYP2C19/CYP2D6 genotyping.Conclusions: Preemptive multi-gene NGS detected more clinically actionable PGx results than targeted CYP2C19/CYP2D6 genotyping. Effective PGx screening in the MHS may decrease preventable adverse effects and improve military readiness.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"637-645"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of genetic and clinical factors on thiopurine drugs pharmacokinetics in Tunisian patients. 遗传和临床因素对突尼斯患者体内硫嘌呤药物药代动力学的影响。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-10-09 DOI: 10.1080/14622416.2024.2406739

Zohra Chadli, Ibtissem Hannachi, Manel Ben Belgacem, Arwa Guediche, Haifa Ben Romdhane, Emna Kerkeni, Lamia Hamdi, Ahlem Slama, Amel Chaabane, Nadia Ben Fredj, Naceur A Boughattas, Leila Safer, Karim Aouam

{"title":"Effects of genetic and clinical factors on thiopurine drugs pharmacokinetics in Tunisian patients.","authors":"Zohra Chadli, Ibtissem Hannachi, Manel Ben Belgacem, Arwa Guediche, Haifa Ben Romdhane, Emna Kerkeni, Lamia Hamdi, Ahlem Slama, Amel Chaabane, Nadia Ben Fredj, Naceur A Boughattas, Leila Safer, Karim Aouam","doi":"10.1080/14622416.2024.2406739","DOIUrl":"10.1080/14622416.2024.2406739","url":null,"abstract":"Aim: Thiopurine drugs are used in the treatment of various diseases including inflammatory bowel disease. Thiopurine-S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) are the crucial enzymes involved in thiopurines metabolism. The present study aims to investigate in Tunisian patients, the influence of genetic and nongenetic factors on thiopurine drugs pharmacokinetics.Experimental approach: We have included patients having received thiopurine drugs and have undergone 6-thioguanine nucleotides (6-TGN) concentration monitoring. The identification of TPMT and ITPA polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The impact of both genetic and nongenetic factors on the variability of the 6-TGN C/D ratio was analyzed through a stepwise multiple regression model.Key results: One hundred and twenty-three patients were included in the study. For TPMT, the most frequent variant allele was TPMT*3B (3.3%). For ITPA, the predominant polymorphism was the c.IVS2 + 21A> C (7%). We have demonstrated that only gender, the TPMT*3A and TPMT*3C alleles are significantly involved on the variability of thiopurines pharmacokinetics.Conclusion: Our study is the first to evaluate, in African patients, the impact of both genetic and nongenetic factors on the thiopurine drugs pharmacokinetics. Considering the narrow therapeutic range of these drugs, TPMT genotyping combined with 6-TGN blood concentration monitoring may enhance their efficacy and safety.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"441-450"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0