Pharmacogenetics and genomics最新文献

{"title":"MiRNA-139-3p inhibits malignant progression in urothelial carcinoma of the bladder via targeting KIF18B and inactivating Wnt/beta-catenin pathway.","authors":"Wenbin Zhang,&nbsp;Zhihua Liu","doi":"10.1097/FPC.0000000000000485","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000485","url":null,"abstract":"<p><strong>Objective: </strong>Bladder cancer is a highly prevalent disease worldwide. We aimed to investigate the effect of miRNA/mRNA signaling on bladder urothelial carcinoma (BUC).</p><p><strong>Methods: </strong>MiRNA-139-3p wasselected from The Cancer Genome Atlas database, and its downstream target gene was predicted. The correlation between miRNA-139-3p and intersected mRNAs was analyzed. The mRNA expression levels of miRNA-139-3p and KIF18B in BUC were assayed via quantitative real-time polymerase chain reaction. Effects of miRNA-139-3p on cell proliferation, invasion, migration and cell cycle were detected via Cell Counting Kit-8, colony formation, transwell, wound healing and flow cytometry assays, respectively. Binding relationship between miRNA-139-3p and KIF18B was verified by dual-luciferase reporter gene detection. The protein expression levels of KIF18B, β-catenin and Cyclin D1 were detected by Western blot. Rescue assays were performed for verifying the interaction among miRNA-139-3p, KIF18B and Wnt/β-catenin signaling pathway, which revealed effects of miRNA-139-3p/KIF18B on BUC cells.</p><p><strong>Results: </strong>MiRNA-139-3p was remarkably underexpressed, and KIF18B was dramatically overexpressed in BUC cells, respectively. It was also demonstrated that overexpressing miRNA-139-3p could prominently inhibit proliferation, invasion and migration of BUC, and block BUC cells at G0-G1 phase. Afterwards, we found that miRNA-139-3p could bind to KIF18B mRNA 3'UTR, and miRNA-139-3p had a negative regulatory effect with KIF18B. Subsequent experimental results presented that overexpressing KIF18B could reverse inhibitory effect of overexpressing miRNA-139-3p on BUC. Finally, this study also ascertained that miRNA-139-3p/KIF18B could repress oncogenic effects of BUC via modulating Wnt/β-catenin signaling pathway.</p><p><strong>Conclusion: </strong>MiRNA-139-3p/KIF18B/Wnt/β-catenin could significantly inhibit the malignant progression of BUC, and its targeting mechanism might provide an effective therapeutic target for BUC patients.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 1","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9115682","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}

{"title":"Impact of organic anion transporting polypeptide, P-glycoprotein, and breast cancer resistance protein transporters on observed tamoxifen and endoxifen concentration and adverse effects.","authors":"Denise N Keller,&nbsp;Samantha J Medwid,&nbsp;Cameron D Ross,&nbsp;Theodore J Wigle,&nbsp;Richard B Kim","doi":"10.1097/FPC.0000000000000486","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000486","url":null,"abstract":"<p><strong>Objective: </strong>Drug transporters are important determinants of drug disposition and response. Tamoxifen is an antiestrogen for breast cancer therapy known for adverse drug reactions (ADRs). In this study, the involvement of OATP transporters in tamoxifen and endoxifen transport was studied in vitro while the impact of single nucleotide variation (SNV) in OATP and efflux transporters P-glycoprotein ( ABCB1 ) and Breast Cancer Resistance Protein ( ABCG2 ) on ADRs during tamoxifen therapy were assessed.</p><p><strong>Methods: </strong>Patients receiving tamoxifen for breast cancer, who were CYP2D6 normal metabolizers were enrolled ( n  = 296). Patients completed a survey that captured ADRs and a blood sample was collected. Tamoxifen and endoxifen plasma concentration were measured, while DNA was genotyped for SNVs in ABCB1, ABCG2, SLCO1A2, SLCO1B1 , and SLCO2B1 . HEK293T cells were used to determine the extent of OATP-mediated transport of tamoxifen and endoxifen.</p><p><strong>Results: </strong>Common SNVs of ABCB1, ABCG2, SLCO1A2 , and SLCO1B1 were not associated with tamoxifen or endoxifen concentration. However, tamoxifen concentration was significantly higher in carriers of SLCO2B1 c.935G>A (129.8 ng/mL) compared to wildtype (114.9 ng/mL; P  = 0.036). Interestingly, subjects who carried SLCO1A2 c.38A>G reported significantly less dizziness ( P  = 0.016). In-vitro analysis demonstrated increased cellular accumulation of tamoxifen in cells overexpressing OATP1A2 and 1B1, but endoxifen uptake was not effected in OATP overexpressing cells.</p><p><strong>Conclusions: </strong>We showed that OATP1A2 , a transporter known to be expressed at the blood-brain barrier, is capable of tamoxifen transport. Additionally, OATP1A2 c.38A>G was associated with reduced ADRs. Taken together, our findings suggest genetic variation in OATP transporters may be an important predictor of tamoxifen ADRs.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 1","pages":"10-18"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10238250","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}

{"title":"Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on prothrombin time and the residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation in real clinical practice.","authors":"Dmitry Alekseevitch Sychev,&nbsp;Aleksey Vladimirovich Sokolov,&nbsp;Olga Vilorovna Reshetko,&nbsp;Vladimir Petrovich Fisenko,&nbsp;Igor Nikolaevich Sychev,&nbsp;Elena Anatolievna Grishina,&nbsp;Pavel Olegovich Bochkov,&nbsp;Roman Vladimirovich Shevchenko,&nbsp;Sherzod Pardaboevich Abdullaev,&nbsp;Natalia Pavlovna Denisenko,&nbsp;Dmitry Vladimirovich Ivashchenko,&nbsp;Zhannet Alimovna Sozaeva,&nbsp;Anastasia Alekseevna Kachanova","doi":"10.1097/FPC.0000000000000483","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000483","url":null,"abstract":"<p><strong>Objective: </strong>The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation.</p><p><strong>Methods: </strong>In total 86 patients (42 men and 44 female), aged 67.24 ± 1.01 years with atrial fibrillation were enrolled in the study. HPLC mass spectrometry analysis was used to determine rivaroxaban residual equilibrium concentration. Prothrombin time data were obtained from patient records.</p><p><strong>Results: </strong>The residual equilibrium concentration of rivaroxaban in patients with ABCB1 rs4148738 CT genotype is significantly higher than in patients with ABCB1 rs4148738 CC (P  = 0.039). The analysis of the combination of genotypes did not find a statistically significant role of combinations of alleles of several polymorphic markers in increasing the risk of hemorrhagic complications when taking rivaroxaban.</p><p><strong>Conclusion: </strong>Patients with ABCB1 rs4148738 CT genotype have a statistically significantly higher residual equilibrium concentration of rivaroxaban in blood than patients with ABCB1 rs4148738 CC genotype, which should be considered when assessing the risk of hemorrhagic complications and risk of drug-drug interactions. Further studies of the effect of rivaroxaban pharmacogenetics on the safety profile and efficacy of therapy are needed.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 9","pages":"301-307"},"PeriodicalIF":2.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9191496","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}

{"title":"Proximal tubular dysfunction related to tenofovir in people living with HIV/AIDS: a pharmacogenetic study.","authors":"Rita De Cassia Albuquerque Soares,&nbsp;Paulo Sérgio Ramos De Araújo,&nbsp;Lucas André Cavalcanti Brandão,&nbsp;Antônio Victor Campos Coelho,&nbsp;Kledoaldo Lima,&nbsp;Heloisa Ramos Lacerda De Melo","doi":"10.1097/FPC.0000000000000482","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000482","url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this case-control study was to verify the association between single nucleotide polymorphisms (SNPs) in genes encoding drug transporters related to tenofovir disoproxil fumarate (TDF) and proximal renal tubular dysfunction (PRTD), and the association between PRTD and clinical characteristics.</p><p><strong>Methods: </strong>The 'cases' met the diagnostic criteria for PRTD, determined by the presence of two or more of the following abnormalities: non-diabetic glycosuria, metabolic acidosis, increased uric acid and phosphorus excretion, decreased tubular phosphorus reabsorption and β2-microglobulinuria. We analyzed eight SNPs in ABCC2, ABCC4, ABCC10 and SLC28A2 genes. Genotyping was performed using real-time PCR.</p><p><strong>Results: </strong>Of the 204 people living with HIV, 38 (18.6%) met the criteria for diagnosis of PRTD and 131 were male (64.2%), with a mean age of 49 years and a history of previous antiretroviral therapy for an average of 5 years. In the multivariate analysis, older individuals, TDF use, protease inhibitor, antihypertensives and anticonvulsants were associated with a risk of developing PRTD. Increased excretion of β2microglobulin was associated with the A/G genotype of rsCC8187710 from ABCC2 ( P  = 0.003) and the following genotypes of ABCC4 SNPs: A/G from rs1059751 ( P  = 0.023), G/G from rs1059751 ( P  = 0.030) and C/C of rs3742106 ( P  = 0.041). The increase in the fraction of excreted phosphorus was associated with the C/T genotype of SNCC rsP40037 from ABCC2 ( P  = 0.0041).</p><p><strong>Conclusions: </strong>The results indicate an important relationship between SNPs associated with these markers and changes in proximal renal tubule function, and thus support their use as biomarkers for the early detection of PRTD risk.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 9","pages":"293-300"},"PeriodicalIF":2.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10638617","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}

{"title":"Body weight changes and bipolar disorder: a molecular pathway analysis.","authors":"Marco Calabró,&nbsp;Silvana Briuglia,&nbsp;Concetta Crisafulli,&nbsp;Antonio Drago","doi":"10.1097/FPC.0000000000000484","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000484","url":null,"abstract":"<p><strong>Background: </strong>There is evidence suggesting a link between weight-related disorders and bipolar disorder (BD). The pathophysiology of the association includes psychological, social and psychotropic treatment-related variables, together with psychiatric comorbidity. Weight changes during BD may influence compliance to the treatment, quality of life and prognosis, and can modulate risk of death associated with, for example, diabetes or cardiovascular disorders.</p><p><strong>Methods: </strong>The STEP-BD sample is analyzed through a hypothesis-free molecular pathway analysis in order to detect the molecular pathways that distinguish individuals who experience weight change during BD treatment from those who do not. A total of 618 individuals were available for the analysis, mean age = 41.19 ± 12.58, females = 351 (56.8%). Socioeconomic variables and treatment-related variables were included as clinical covariates. A cluster analysis in the genetic dataset provided the genetic covariate input to the study to avoid stratification factors.</p><p><strong>Result: </strong>After applying the quality analysis that is typical for this kind of investigation, no Genome Wide Association Study significant finding was retrieved. Six molecular pathways were found to be significantly associated with weight change during the first 3 months of treatment after correction for multiple testing. Of those, CDC42 (R-HSA-9013148) participates in insulin synthesis and secretion and contributes to the pathogenesis of insulin resistance and Rac Family Small GTPase 1 (R-HSA-9013149) is involved in metabolic regulation of pancreatic islet β-cells and in diabetes pathophysiology.</p><p><strong>Discussion: </strong>Pathways that are central in energy homeostasis may play a role to separate individuals with BD that will experience weight changes during treatment from those who will not. If confirmed, such finding can be instrumental in the identification of the correct preventive strategies and most correct treatment to increase compliance and efficacy in the treatment of BD.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"308-320"},"PeriodicalIF":2.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40434846","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}

{"title":"Influence of MDR1 gene polymorphism (2677G>T) on expression and function of P-glycoprotein at the blood-brain barrier: utilizing novel P-glycoprotein humanized mice with mutation.","authors":"Yuki Yamasaki,&nbsp;Takashi Moriwaki,&nbsp;Seiryo Ogata,&nbsp;Shingo Ito,&nbsp;Sumio Ohtsuki,&nbsp;Genki Minegishi,&nbsp;Satoshi Abe,&nbsp;Yumi Ohta,&nbsp;Kanako Kazuki,&nbsp;Kaoru Kobayashi,&nbsp;Yasuhiro Kazuki","doi":"10.1097/FPC.0000000000000481","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000481","url":null,"abstract":"<p><p>P-glycoprotein, the encoded product of the MDR1 / ABCB1 gene in humans, is expressed in numerous tissues including brain capillary endothelial cells and restricts the distribution of xenobiotics into the brain as an efflux pump. Although a large number of single nucleotide polymorphisms in the MDR1 gene have been identified, the influence of the nonsynonymous 2677G>T/A single nucleotide polymorphism on P-glycoprotein at the blood-brain barrier has remained unclear. In the present study, we developed a novel P-glycoprotein humanized mouse line carrying the 2677G>T mutation by utilizing a mouse artificial chromosome vector constructed by genetic engineering technology and we evaluated the influence of 2677G>T on the expression and function of P-glycoprotein at the blood-brain barrier in vivo . The results of this study showed that the introduction of the 2677G>T mutation does not alter the expression levels of P-glycoprotein protein in the brain capillary fraction. On the other hand, the brain penetration of verapamil, a representative substrate of P-glycoprotein, was increased by the introduction of the 2677G>T mutation. These results suggested that the 2677G>T single nucleotide polymorphism may attenuate the function of P-glycoprotein, resulting in increased brain penetration of P-glycoprotein substrates, without altering the expression levels of P-glycoprotein protein in the blood-brain barrier. This mutant mouse line is a useful model for elucidating the influence of an MDR1 gene single nucleotide polymorphism on the expression and function of P-glycoprotein at the blood-brain barrier.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 8","pages":"288-292"},"PeriodicalIF":2.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10544110","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}

{"title":"Attitudes on pharmacogenomic results as secondary findings among medical geneticists.","authors":"Meghan N Bartos,&nbsp;Stuart A Scott,&nbsp;Ethylin Wang Jabs,&nbsp;Hetanshi Naik","doi":"10.1097/FPC.0000000000000479","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000479","url":null,"abstract":"<p><strong>Objectives: </strong>As evidence mounts supporting the utility of pharmacogenomic-guided medication management, incorporating pharmacogenomic genes into secondary finding results from sequencing panels is increasingly under consideration. We studied medical geneticists' attitudes on receiving pharmacogenomic results as secondary finding.</p><p><strong>Methods: </strong>Four focus groups with 16 medical geneticists total were conducted followed by thematic analysis.</p><p><strong>Results: </strong>All participants ordered genetic sequencing tests; however, the majority had rarely or never ordered pharmacogenomic tests (10/16) or prescribed medications with established response variability (11/16). In total 81.3% expressed low comfort interpreting pharmacogenomic results without appropriate clinical resources (13/16). The positives of receiving pharmacogenomic results as secondary finding included prevention of adverse drug reactions in adults, grateful information-seeking patients, the ability to rapidly prescribe more effective treatments and appreciation of the recent advances in both pharmacogenomic knowledge and available guidelines. Negatives included laboratory reporting issues, exclusivity of pharmacogenomic results to certain populations, lengthy reports concealing pharmacogenomic results in patient charts and laboratories marketing to individuals without prior pharmacogenomic knowledge or targeting inappropriate populations. The most desirable pharmacogenomic resources included a universal electronic health record clinical decision support tool to assist identifying and implementing pharmacogenomic results, a specialized pharmacist as part of the care team, additional pharmacogenomic training during medical/graduate school, and a succinct interpretation of pharmacogenomic results included on laboratory reports.</p><p><strong>Conclusions: </strong>The majority of participants agreed that adding certain actionable pharmacogenomic genes to the American College of Medical Genetics and Genomics SF list is reasonable; however, this was qualified with a need for additional resources to support implementation.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 8","pages":"273-280"},"PeriodicalIF":2.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10189825","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}

{"title":"Association of ATP8B3 gene polymorphisms with aspirin-exacerbated respiratory disease in asthmatics.","authors":"Jong-Uk Lee,&nbsp;Min Kyung Kim,&nbsp;Seung-Lee Park,&nbsp;Da Jeong Bae,&nbsp;Hun Soo Chang,&nbsp;Choon-Sik Park,&nbsp;Jong Sook Park","doi":"10.1097/FPC.0000000000000480","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000480","url":null,"abstract":"<p><strong>Background: </strong>Aspirin-exacerbated respiratory disease (AERD), an asthma phenotype, often presents with severe manifestations and it remains widely underdiagnosed because of insufficient awareness of the relationship between the ingestion of nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid (ASA), and asthma exacerbation. Our previous genome-wide association study demonstrated an association between a single nucleotide polymorphism (SNP) of the ATP8B3 gene and the risk of AERD. This study examined AERD-related SNPs of the ATP8B3 gene in a large population.</p><p><strong>Methods: </strong>Twenty-five SNPs of ATP8B3 were genotyped with the GoldenGate assay using VeraCode microbeads in 141 asthmatics with AERD and 995 Aspirin-tolerant asthma (ATA). The genotype distribution was analyzed using logistic regression models. The declines in forced expiratory volume in 1 second (FEV1)following an ASA challenge were compared among the genotypes and haplotypes using a type III generalized linear model.</p><p><strong>Results: </strong>The minor allele frequencies (MAFs) of rs10421558 A>G in the 5'UTR and rs10403288 G>A in the intron were significantly lower in the AERD than the ATA [34.0% vs. 43.8%, OR = 0.66 (0.62-0.92), Pcorr = 0.03 and 28.4% vs. 35.4%, OR = 0.62 (0.59-0.89), Pcorr = 0.016, respectively]. BL1ht5 was significantly higher in the AERD [7.6% vs. 1.6%, OR = 12.23 (0.2-0.51), P = 4.7 × 10 -4 , Pcorr = 0.001]. Among them, rs10421558 A>G and BL1ht5 were associated with the percent decline in FEV1 on the oral ASA challenge test.</p><p><strong>Conclusion: </strong>The minor allele of rs10421558 A>G in the 5'UTR may protect against the development of AERD via the increased production of ATP8B3.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 8","pages":"281-287"},"PeriodicalIF":2.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10563096","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}

{"title":"Impact of cytochrome P450 2C19 polymorphisms on the clinical efficacy and safety of voriconazole: an update systematic review and meta-analysis.","authors":"Ying Zhang,&nbsp;Xu Hao,&nbsp;Kelu Hou,&nbsp;Lei Hu,&nbsp;Jingyuan Shang,&nbsp;Shiyu He,&nbsp;Changqing Yang,&nbsp;Lin Huang,&nbsp;Yufei Feng","doi":"10.1097/FPC.0000000000000470","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000470","url":null,"abstract":"<p><strong>Objective: </strong>To assess the impact of cytochrome P450 (CYP) 2C19 polymorphisms on the clinical efficacy and safety of voriconazole.</p><p><strong>Methods: </strong>We systematically searched PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases from their inception to 18 March 2021 using a predefined search algorithm to identify relevant studies. Studies that reported voriconazole-treated patients and information on CYP2C19 polymorphisms were included. The efficacy outcome was success rate. The safety outcomes included overall adverse events, hepatotoxicity, and neurotoxicity.</p><p><strong>Results: </strong>A total of 20 studies were included. Intermediate metabolizers (IMs) and poor metabolizers (PMs) were associated with increased success rates compared with normal metabolizers (NMs) [risk ratio (RR), 1.18; 95% confidence interval (CI), 1.03-1.34; I2 = 0%; P = 0.02; RR, 1.28; 95% CI, 1.06-1.54; I2 = 0%; P = 0.01]. PMs were at increased risk of overall adverse events in comparison with NMs and IMs (RR, 2.18; 95% CI, 1.35-3.53; I2 = 0%; P = 0.001; RR, 1.80; 95% CI, 1.23-2.64; I2 = 0%; P = 0.003). PMs demonstrated a trend towards an increased incidence of hepatotoxicity when compared with NMs (RR, 1.60; 95% CI, 0.94-2.74; I2 = 27%; P = 0.08), although there was no statistically significant difference. In addition, there was no significant association between CYP2C19 polymorphisms and neurotoxicity.</p><p><strong>Conclusion: </strong>IMs and PMs were at a significant higher success rate in comparison with NMs. PMs were significantly associated with an increased incidence of all adverse events compared with NMs and IMs. Researches are expected to further confirm these findings. Additionally, the relationship between hepatotoxicity and CYP2C19 polymorphisms deserves clinical attention.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"257-267"},"PeriodicalIF":2.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40682758","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}

{"title":"Investigation of pharmacologic interactions between omeprazole and tacrolimus in a membranous nephropathy patient with CYP3A5 nonexpresser: a case report.","authors":"Yanli Li,&nbsp;Yi Liu,&nbsp;Zengxian Sun","doi":"10.1097/FPC.0000000000000478","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000478","url":null,"abstract":"<p><p>Tacrolimus has been widely used in membranous nephropathy in recent years. The drug interactions of the coadministration of tacrolimus with omeprazole in CYP3A5 nonexpresser membranous nephropathy patients have not been demonstrated. Here, we report an idiopathic membranous nephropathy patient who was with CYP2C19*2/*2, CYP3A5*3/*3 (nonexpresser) and ABCB1 (3435 TT, 1236 computed tomography, 2677 TT) genotype requiring treatment with tacrolimus and omeprazole and found to have fluctuating metabolism of tacrolimus. This study shows that tacrolimus and omeprazole have pharmacologic drug interactions in CYP3A5 nonexpressers, implying that the CYP3A and ABCB1 gene mutations linked to tacrolimus metabolism may alter tacrolimus levels in the blood. The observed concentrations of tacrolimus were decreased after the discontinuation of omeprazole therapy. It demonstrates that, in addition to genotype, clinical covariates, such as omeprazole are important when it comes to better understanding and prediction of tacrolimus dosage. It is deemed necessary to monitor tacrolimus blood concentrations and make dose adjustments when patients were coadministered with omeprazole.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"32 7","pages":"268-271"},"PeriodicalIF":2.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10582991","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}