Pharmacogenomics最新文献_第6页

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

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

TPMT and NUDT15 genotyping, TPMT enzyme activity and metabolite determination for thiopurines therapy: a reference laboratory experience. 硫嘌呤治疗的TPMT和NUDT15基因分型，TPMT酶活性和代谢物测定：参考实验室经验。

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

Providers' use of pharmacogenetic testing to inform opioid prescribing among veterans. 医疗机构利用药物基因检测为退伍军人开具阿片类药物处方提供信息。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-10-09 DOI: 10.1080/14622416.2024.2409058

Rachele K Lipsky, Catherine Chanfreau-Coffinier, Deepak Voora, Jodie Trafton, Charlotte Williams, Susana B Martins, Sumitra Muralidhar, David W Oslin

{"title":"Providers' use of pharmacogenetic testing to inform opioid prescribing among veterans.","authors":"Rachele K Lipsky, Catherine Chanfreau-Coffinier, Deepak Voora, Jodie Trafton, Charlotte Williams, Susana B Martins, Sumitra Muralidhar, David W Oslin","doi":"10.1080/14622416.2024.2409058","DOIUrl":"10.1080/14622416.2024.2409058","url":null,"abstract":"Aim: To survey Veterans Health Administration providers who prescribed tramadol or codeine to patients with known genotyping for cytochrome 2D6 (CYP2D6) to ascertain awareness of their patient's pharmacogenetic (PGx) test status, whether these results influenced prescribing, perceived benefit of PGx testing, and resources needed to obtain and deliver PGx testing information.Materials & methods: A provider survey was conducted of those who prescribed tramadol or codeine in a patient genotyped for CYP2D6.Results: Of 876 eligible providers, 220 completed the survey. Ten percent were aware that their patient received a PGx test, 64% had not ordered any PGx test related to any medication in the prior year, 55% strongly agreed or agreed that PGx testing is or will be valuable to guide pain medication prescriptions, 29% felt that the evidence base for PGx testing is very strong or moderately strong, 22% responded likely or extremely likely to order a future PGx test, and 51% felt that it would be either very important or fairly important to have a local subject matter expert as a resource for PGx testing.Conclusion: There are modifiable factors that the Veterans Health Administration could address to optimize PGx testing for pain management.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"495-501"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392334","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

Meta-analysis revisiting the influence of UGT1A1*28 and UGT1A1*6 on irinotecan safety in colorectal cancer patients. 重新审视 UGT1A1*28 和 UGT1A1*6 对结直肠癌患者伊立替康安全性影响的 Meta 分析。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-08-22 DOI: 10.1080/14622416.2024.2385289

Cuc Thi Thu Nguyen, Thi Minh Thuy Nguyen, Thanh Huong Phung

{"title":"Meta-analysis revisiting the influence of UGT1A1*28 and UGT1A1*6 on irinotecan safety in colorectal cancer patients.","authors":"Cuc Thi Thu Nguyen, Thi Minh Thuy Nguyen, Thanh Huong Phung","doi":"10.1080/14622416.2024.2385289","DOIUrl":"10.1080/14622416.2024.2385289","url":null,"abstract":"Aim: To evaluate the association between irinotecan safety and the UGT1A1 gene polymorphism in colorectal cancer (CRC) patients.Materials & methods: The studies were systematically searched and identified from three databases (PubMed, Embase and The Cochrane Library) until 28 February 2023. The relationships were evaluated using pooled odds ratio (OR).Results: A total of 30 studies out of 600 were included, comprising 4471 patients. UGT1A1*28 was associated with a statistically significant increase in the OR for diarrhea (OR: 1.59, 95% CI = 1.24-2.06 in the additive model; OR = 3.24, 95% CI = 2.01-5.21 in the recessive model; and OR = 1.95, 95% CI = 1.42-2.69 in the dominant model) and neutropenia (OR = 1.70, 95% CI = 1.40-2.06 in the additive model; OR = 4.10, 95%CI = 2.69-6.23 in the recessive model; and OR = 1.93, 95% CI = 1.61-2.31 in the dominant model). Subgroup analysis indicated consistent associations in both Asian and non-Asian populations. UGT1A1*6 was associated with a statistically significant elevation in the OR for diarrhea (only in the recessive model, OR = 2.42; 95% CI = 1.14-5.11) and neutropenia (across all genetic models).Conclusion: The UGT1A1*28 and UGT1A1*6 alleles might be a crucial indicator for predicting irinotecan safety in CRC.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"469-477"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018282","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

Pharmacogenetic markers and macrolide safety in influenza patients: insights from a prospective study. 流感患者的药物遗传标记和大环内酯安全性：来自一项前瞻性研究的见解。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-01-19 DOI: 10.1080/14622416.2025.2454217

A A Skryabina, V V Nikiforov, M Z Shakhmardanov, M S Zastrozhin, D A Sychev

{"title":"Pharmacogenetic markers and macrolide safety in influenza patients: insights from a prospective study.","authors":"A A Skryabina, V V Nikiforov, M Z Shakhmardanov, M S Zastrozhin, D A Sychev","doi":"10.1080/14622416.2025.2454217","DOIUrl":"10.1080/14622416.2025.2454217","url":null,"abstract":"Background: Macrolides are widely used antibiotics, but adverse drug reactions (ADRs), particularly in genetically predisposed individuals, can compromise their safety. This study examines the impact of pharmacogenetic markers on macrolide safety in participants with bacterial complications of influenza.Objective: To evaluate how polymorphisms in genes encoding transporter proteins (ABCB1) and enzymes (CYP3A4, CYP3A5) influence ADR risk during macrolide therapy.Methods: A prospective study included 100 participants with lower respiratory tract bacterial complications of influenza treated with azithromycin or erythromycin for five days. Genotyping targeted ABCB1 (3435C>T), CYP3A4 (C>T intron 6), and CYP3A5 (6986A>G) polymorphisms. ADRs were monitored daily and correlated with genetic markers.Results: The ABCB1 (3435C>T) polymorphism was associated with higher rates of abdominal pain and diarrhea in CT and TT genotypes (OR = 2.12, p = 0.043). The CYP3A4 (C>T intron 6) polymorphism increased ADR risk in erythromycin-treated participants (OR = 24.0, p = 0.0339). No significant effects were observed for CYP3A5 (6986A>G).Conclusion: Genetic polymorphisms in ABCB1 and CYP3A4 genes predict macrolide-related ADRs. Pharmacogenetic screening could improve macrolide safety, particularly for genetically susceptible individuals.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"661-665"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009703","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

Effect of UGT1A6 and UGT2B7 polymorphisms on the valproic acid serum concentration and drug-induced liver injury. UGT1A6 和 UGT2B7 多态性对丙戊酸血清浓度和药物性肝损伤的影响

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-11-20 DOI: 10.1080/14622416.2024.2409061

Mengchen Yu, Yan Zhao, Fan Zhou, Weiliang Li, Jing Liu, Linlin Zhao, Zhirui Song, Ling Tong, Ying Zhang, Yajuan Wang, Shenglan Shang, Airong Yu

{"title":"Effect of UGT1A6 and UGT2B7 polymorphisms on the valproic acid serum concentration and drug-induced liver injury.","authors":"Mengchen Yu, Yan Zhao, Fan Zhou, Weiliang Li, Jing Liu, Linlin Zhao, Zhirui Song, Ling Tong, Ying Zhang, Yajuan Wang, Shenglan Shang, Airong Yu","doi":"10.1080/14622416.2024.2409061","DOIUrl":"10.1080/14622416.2024.2409061","url":null,"abstract":"Aim: Valproic acid (VPA) is a classic broad-spectrum antiepileptic drug, with significant pharmacokinetic variability. Genetic polymorphisms contribute to this variability, influencing both VPA trough serum concentration (VPA concentration) and VPA-induced liver injury. Our study aims to investigate the association between polymorphisms of uridine diphosphate glucuronyl transferase (UGT) 1A6, UGT2B7 and VPA concentration and screen for potential genetic loci affecting VPA-induced liver injury.Methods: This study included epilepsy patients treated with VPA. PCR-RFLP method was used to determine the genotypes of UGT1A6 and UGT2B7. Chemiluminescent microparticle immunoassay was used to measure VPA concentration. Multiple linear regression and logistic regression were employed to analyze factors influencing VPA concentration and VPA-induced liver injury, respectively.Results: The correlation between UGT polymorphism and VPA concentration was analyzed in 133 samples. For VPA-induced liver injury, 105 patients were analyzed, with 29 in the liver injury group and 76 in the control group. Our finding showed patients with the UGT1A6-T19G variant had significantly lower VPA concentrations compared with wild-type patients and UGT1A6-T19G, A541G, A552C and UGT2B7-C802T, G211T, A268G polymorphisms showed no impact on VPA-induced liver injury.Conclusion: This study demonstrated UGT1A6-T19G polymorphisms affected the VPA concentration, providing a theoretical basis for the individualized clinical use of VPA.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"527-538"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676500","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

It is time for educators to act: pharmacogenomics education and its implementation into clinical practice. 现在是教育工作者采取行动的时候了：药物基因组学教育及其在临床实践中的实施。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-09-04 DOI: 10.1080/14622416.2024.2392482

Snezana Kusljic, Jasmine A Luzum

引用次数: 0