Pharmacogenomics Journal最新文献_第2页

Extreme phenotype sampling and next generation sequencing to identify genetic variants associated with tacrolimus in African American kidney transplant recipients 通过极端表型取样和新一代测序技术，确定非裔美国肾移植受者中与他克莫司相关的基因变异。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-23 DOI: 10.1038/s41397-024-00349-8

Moataz E. Mohamed, Bin Guo, Baolin Wu, David P. Schladt, Amutha Muthusamy, Weihua Guan, Juan E. Abrahante, Guillaume Onyeaghala, Abdelrahman Saqr, Nathan Pankratz, Gaurav Agarwal, Roslyn B. Mannon, Arthur J. Matas, William S. Oetting, Rory P. Remmel, Ajay K. Israni, Pamala A. Jacobson, DeKAF Genomics and GEN03 Investigators, Casey R. Dorr

{"title":"Extreme phenotype sampling and next generation sequencing to identify genetic variants associated with tacrolimus in African American kidney transplant recipients","authors":"Moataz E. Mohamed, Bin Guo, Baolin Wu, David P. Schladt, Amutha Muthusamy, Weihua Guan, Juan E. Abrahante, Guillaume Onyeaghala, Abdelrahman Saqr, Nathan Pankratz, Gaurav Agarwal, Roslyn B. Mannon, Arthur J. Matas, William S. Oetting, Rory P. Remmel, Ajay K. Israni, Pamala A. Jacobson, DeKAF Genomics and GEN03 Investigators, Casey R. Dorr","doi":"10.1038/s41397-024-00349-8","DOIUrl":"10.1038/s41397-024-00349-8","url":null,"abstract":"African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n = 58) and low (n = 60) TAC troughs (N = 515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12 mg, respectively. Of 34,542 identified variants across 99 genes, 1406 variants were suggestively associated with TAC troughs in univariate models (p-value < 0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

STRIPE partners in precision medicine series: provider perspective STRIPE 合作伙伴精准医疗系列：医疗服务提供者视角。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-23 DOI: 10.1038/s41397-024-00348-9

Christine M. Formea, Paldeep Atwal, Kathryn Meintsma, Martin Dawes, Gary Marchant, Ben L. Kong, J. Shawn Jones, Sara L. Rogers

引用次数: 0

A collaborative force for precision medicine progress: the STRIPE pharmacogenomics conference series 精准医学进步的合作力量：STRIPE 药物基因组学系列会议。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-15 DOI: 10.1038/s41397-024-00345-y

Sara L. Rogers, J. Shawn Jones, Ben L. Kong, Christine M. Formea, Jacob Awkal, Benjamin G. Brown

引用次数: 0

STRIPE partners in precision medicine series: pharmacist perspective STRIPE 合作伙伴精准医疗系列：药剂师视角。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-14 DOI: 10.1038/s41397-024-00347-w

Ben L. Kong, Roseann S. Donnelly, Amina Abubakar, Henry M. Dunnenberger, J. Shawn Jones, Sara L. Rogers, David Kisor

引用次数: 0

Understanding general practitioner and pharmacist preferences for pharmacogenetic testing in primary care: a discrete choice experiment 了解全科医生和药剂师对基层医疗机构药物基因检测的偏好：离散选择实验。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-09 DOI: 10.1038/s41397-024-00344-z

John H. McDermott, Videha Sharma, Glenda M. Beaman, Jessica Keen, William G. Newman, Paul Wilson, Katherine Payne, Stuart Wright

{"title":"Understanding general practitioner and pharmacist preferences for pharmacogenetic testing in primary care: a discrete choice experiment","authors":"John H. McDermott, Videha Sharma, Glenda M. Beaman, Jessica Keen, William G. Newman, Paul Wilson, Katherine Payne, Stuart Wright","doi":"10.1038/s41397-024-00344-z","DOIUrl":"10.1038/s41397-024-00344-z","url":null,"abstract":"Pharmacogenetic testing in the United Kingdom’s National Health Service (NHS) has historically been reactive in nature, undertaken in the context of single gene-drug relationships in specialist settings. Using a discrete choice experiment we aimed to identify healthcare professional preferences for development of a pharmacogenetic testing service in primary care in the NHS. Respondents, representing two professions groups (general practitioners or pharmacists), completed one of two survey versions, asking them to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or joint pain. Responses from 235 individuals were included. All respondents preferred pharmacogenetic testing over no testing, though preference heterogeneity was identified. Both professional groups, but especially GPs, were highly sensitive to service design, with uptake varying depending on the service offered. This study demonstrates uptake of a pharmacogenetic testing service is impacted by service design and highlights key areas which should be prioritised within future initiatives.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-7"},"PeriodicalIF":2.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Unveiling the association between HMG-CoA reductase inhibitors and bladder cancer: a comprehensive analysis using Mendelian randomization, animal models, and transcriptomics 揭示 HMG-CoA 还原酶抑制剂与膀胱癌之间的关联：利用孟德尔随机化、动物模型和转录组学进行综合分析。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-07 DOI: 10.1038/s41397-024-00346-x

Houyi Wei, Zhilong Li, Kaiyu Qian, Wenzhi Du, Lingao Ju, Danni Shan, Mengxue Yu, Yayun Fang, Yi Zhang, Yu Xiao, Gang Wang, Xinghuan Wang

{"title":"Unveiling the association between HMG-CoA reductase inhibitors and bladder cancer: a comprehensive analysis using Mendelian randomization, animal models, and transcriptomics","authors":"Houyi Wei, Zhilong Li, Kaiyu Qian, Wenzhi Du, Lingao Ju, Danni Shan, Mengxue Yu, Yayun Fang, Yi Zhang, Yu Xiao, Gang Wang, Xinghuan Wang","doi":"10.1038/s41397-024-00346-x","DOIUrl":"10.1038/s41397-024-00346-x","url":null,"abstract":"This study utilized Mendelian randomization (MR) analysis and genome-wide association study (GWAS) data to investigate the association between commonly prescribed drugs and bladder cancer (BLCA) risk. Our results revealed that HMG CoA reductase (HMGCR) inhibitors, specifically simvastatin, are significantly associated with reduced BLCA risk. We further showed that simvastatin could significantly inhibit BLCA proliferation and epithelial-mesenchymal transition in animal models, with transcriptomic data identifying several pathways associated with these processes. Higher expression of HMGCR were linked with BLCA development and progression, and certain blood lipids, such as lipoprotein particles and very low density lipoprotein (VLDL) cholesterol, might influence BLCA risk. These findings suggested that HMGCR inhibitors, particularly simvastatin, could be potential treatment options or adjuvant therapies for BLCA.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Opioid use disorder risk alleles in self-reported assigned African American/Afro-Caribbean and European biogeographical genetic ancestry groups and in males and females 非裔美国人/非裔加勒比人和欧洲人生物地理遗传血统群体以及男性和女性中自我报告的阿片类药物使用障碍风险等位基因。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-01 DOI: 10.1038/s41397-024-00337-y

Jon E. Sprague, Caroline E. Freiermuth, Joshua Lambert, Robert Braun, Jennifer A. Frey, Daniel J. Bachmann, Jason J. Bischof, Lauren Beaumont, Michael S. Lyons, Michael V. Pantalon, Brittany E. Punches, Rachel Ancona, David F. Kisor

{"title":"Opioid use disorder risk alleles in self-reported assigned African American/Afro-Caribbean and European biogeographical genetic ancestry groups and in males and females","authors":"Jon E. Sprague, Caroline E. Freiermuth, Joshua Lambert, Robert Braun, Jennifer A. Frey, Daniel J. Bachmann, Jason J. Bischof, Lauren Beaumont, Michael S. Lyons, Michael V. Pantalon, Brittany E. Punches, Rachel Ancona, David F. Kisor","doi":"10.1038/s41397-024-00337-y","DOIUrl":"10.1038/s41397-024-00337-y","url":null,"abstract":"The influence of genetic variants related to opioid use disorder (OUD) was evaluated using multiple logistic regression analysis in self-reported assigned African American/Afro-Caribbean and European biogeographical ancestry groups (BGAGs) and by sex. From a sample size of 1301 adult patients (>18 years of age) seen in emergency departments of three medical centers in Ohio, six variants were found to be associated with OUD. Two of the variants, rs2740574 (CYP3A4) and rs324029 (DRD3), were included in the analysis having met criteria of at least five subjects for each BGAG, variant carrier status, and OUD status combinations. Variant carriers in the African/Afro-Caribbean BGAG had slightly lower predicted probabilities of OUD. Variant carriers in the European BGAG had slightly higher predicted probabilities of OUD. Relative to sex, all the six variants met evaluation criteria (five subjects for all sex, variant, and OUD status combinations). No statistically significant interactions were found between a given variant, BGAGs and sex. Findings suggest variant testing relative to OUD risk can be applied across BGAGs and sex, however, studies in larger populations are needed.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 4","pages":"1-6"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Contribution of plasma levels of VEGF-A and angiopoietin-2 in addition to a genetic variant in KCNAB1 to predict the risk of bevacizumab-induced hypertension 除 KCNAB1 基因变异外，血浆中 VEGF-A 和血管生成素-2 水平也有助于预测贝伐珠单抗诱发高血压的风险。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-07-12 DOI: 10.1038/s41397-024-00342-1

Julia C. F. Quintanilha, William Kevin Kelly, Federico Innocenti

{"title":"Contribution of plasma levels of VEGF-A and angiopoietin-2 in addition to a genetic variant in KCNAB1 to predict the risk of bevacizumab-induced hypertension","authors":"Julia C. F. Quintanilha, William Kevin Kelly, Federico Innocenti","doi":"10.1038/s41397-024-00342-1","DOIUrl":"10.1038/s41397-024-00342-1","url":null,"abstract":"Bevacizumab-induced hypertension poses a therapeutic challenge and identifying biomarkers for hypertension can enhance therapy safety. Lower plasma levels of VEGF-A, angiopoietin-2, and rs6770663 in KCNAB1 were previously associated with increased risk of bevacizumab-induced hypertension. This study investigated whether these factors independently contribute to grade 2–3 bevacizumab-induced hypertension risk in 277 cancer patients (CALGB/Alliance 90401). Multivariable analyses assessed the independent association of each factor and hypertension. Likelihood ratio test (LRT) evaluated the explanatory significance of combining protein levels and rs6770663 in predicting hypertension. Boostrap was employed to assess the mediation effect of protein levels on the rs6770663 association with hypertension. Lower protein levels and rs6770663 were independently associated with increased hypertension risk. Adding rs6770663 to protein levels improved the prediction of hypertension (LRT p = 0.0002), with no mediation effect observed. Protein levels of VEGF-A, angiopoietin-2 and rs6770663 in KCNAB1 are independent risk factors and, when combined, may improve prediction of bevacizumab-induced hypertension. ClinicalTrials.gov Identifier: NCT00110214.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 4","pages":"1-4"},"PeriodicalIF":2.9,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-024-00342-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Risk of anthracycline-induced cardiac dysfunction in adolescent and young adult (AYA) cancer survivors: role of genetic susceptibility loci 青少年癌症幸存者中蒽环类药物诱发心功能障碍的风险：遗传易感基因位点的作用。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-06-29 DOI: 10.1038/s41397-024-00343-0

Lily K. Stafford, Xiaohui Tang, Amanda Brandt, Jianzhong Ma, Jose Banchs, J. Andrew Livingston, Michael E. Roth, Alanna C. Morrison, Michelle A. T. Hildebrandt

{"title":"Risk of anthracycline-induced cardiac dysfunction in adolescent and young adult (AYA) cancer survivors: role of genetic susceptibility loci","authors":"Lily K. Stafford, Xiaohui Tang, Amanda Brandt, Jianzhong Ma, Jose Banchs, J. Andrew Livingston, Michael E. Roth, Alanna C. Morrison, Michelle A. T. Hildebrandt","doi":"10.1038/s41397-024-00343-0","DOIUrl":"10.1038/s41397-024-00343-0","url":null,"abstract":"There is a known genetic susceptibility to anthracycline-induced cardiac dysfunction in childhood cancer survivors, but this has not been adequately shown in adolescent and young adult (AYA) patients. Our aim was to determine if the previously identified variants associated with cardiac dysfunction in childhood cancer patients affect AYA cancer patients similarly. Forty-five variants were selected for analysis in 253 AYAs previously treated with anthracyclines. We identified four variants that were associated with cardiac dysfunction: SLC10A2:rs7319981 (p = 0.017), SLC22A17:rs4982753 (p = 0.019), HAS3:rs2232228 (p = 0.023), and RARG:rs2229774 (p = 0.050). HAS3:rs2232228 and SLC10A2:rs7319981 displayed significant effects in our AYA cancer survivor population that were in the opposite direction than that reported in childhood cancer survivors. Genetic variants in the host genes were further analyzed for additional associations with cardiotoxicity in AYA cancer survivors. The host genes were then evaluated in a panel of induced pluripotent stem cell-derived cardiomyocytes to assess changes in levels of expression when treated with doxorubicin. Significant upregulation of HAS3 and SLC22A17 expression was observed (p < 0.05), with non-significant anthracycline-responsivity observed for RARG. Our study demonstrates that there is a genetic influence on cardiac dysfunction in AYA cancer patients, but there may be a difference in the role of genetics between childhood and AYA cancer survivors.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 4","pages":"1-7"},"PeriodicalIF":2.9,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Predictive role of ITPA genetic variants in thiopurine-related myelotoxicity in Crohn’s disease patients ITPA 基因变异在克罗恩病患者硫嘌呤相关骨髓毒性中的预测作用。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-06-21 DOI: 10.1038/s41397-024-00341-2

Juliana Salazar, Pau Riera, Jordi Gordillo, Albert Altès, Miguel Martínez, Montserrat Serès, Jordina Llaó, Antonio Giordano, Esther Garcia-Planella

{"title":"Predictive role of ITPA genetic variants in thiopurine-related myelotoxicity in Crohn’s disease patients","authors":"Juliana Salazar, Pau Riera, Jordi Gordillo, Albert Altès, Miguel Martínez, Montserrat Serès, Jordina Llaó, Antonio Giordano, Esther Garcia-Planella","doi":"10.1038/s41397-024-00341-2","DOIUrl":"10.1038/s41397-024-00341-2","url":null,"abstract":"Thiopurines, an effective therapy for Crohn’s disease (CD), often lead to adverse events (AEs). Gene polymorphisms affecting thiopurine metabolism may predict AEs. This retrospective study in CD patients (n = 114) with TPMT activity > 5 Units/Red Blood Cells analyzed TPMT (c.238 G > C, c.460 G > A, c.719 A > G), ITPA (c.94 C > A, IVS2 + 21 A > C), and NUDT15 (c.415 C > T) polymorphisms. All patients received azathioprine (median dose 2.2 mg/kg) with 41.2% experiencing AEs, mainly myelotoxicity (28.1%). No NUDT15 polymorphisms were found, 7% had TPMT, and 31.6% had ITPA polymorphisms. AEs led to therapy modifications in 41.2% of patients. Multivariate analysis identified advanced age (OR 1.046, p = 0.007) and ITPA IVS2 + 21 A > C (OR 3.622, p = 0.015) as independent predictors of AEs. IVS2 + 21 A > C was also associated with myelotoxicity (OR 2.863, p = 0.021). These findings suggest that ITPA IVS2 + 21 A > C polymorphism and advanced age predict AEs during thiopurine therapy for CD with intermediate-normal TPMT activity.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 4","pages":"1-6"},"PeriodicalIF":2.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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