Pharmacogenetics and genomics最新文献

{"title":"Pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) in newly diagnosed Indian type 2 diabetes patients undergoing metformin monotherapy.","authors":"Shalini Singh,&nbsp;Ashwin Kumar Shukla,&nbsp;Kauser Usman,&nbsp;Monisha Banerjee","doi":"10.1097/FPC.0000000000000493","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000493","url":null,"abstract":"<p><strong>Objectives: </strong>Type 2 diabetes (T2D) imposes an enormous burden all over the world in both developed and developing countries. Inter-individual differences are attributed to polymorphisms in candidate genes resulting in altered absorption, transportation, distribution, and metabolism of oral antidiabetic drugs (OADs). Hence, the present study was undertaken to evaluate the pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) on metformin monotherapy in newly diagnosed untreated T2D patients.</p><p><strong>Methods: </strong>Newly diagnosed T2D patients ( n  = 500) were enrolled according to inclusion/exclusion criteria. Initially, enrolled subjects were prescribed metformin monotherapy and followed up for at least 12 weeks. Response to metformin was evaluated in 478 patients who revisited for follow-up by measuring HbA1c.</p><p><strong>Result: </strong>Out of 478 patients, 373 were responders to metformin monotherapy while 105 were non-responders. The pharmacogenetic impact was evaluated by genotype, haplotype, and pharmacogenetic analyses. 'GG' genotype and 'G' allele of SLC22A1 rs628031 G/A were observed in 48.8% and 67.7% of Met responders, respectively, while 20.9% and 49.1 % were in non-responders. Therefore, there was a 2.18-fold increase in the success rate of Met therapeutics.</p><p><strong>Conclusion: </strong>Individuals carrying the 'GG' genotype or 'G' allele for SLC22A1 gene variant rs628031 G/A are better responders for Metformin monotherapy.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 3","pages":"51-58"},"PeriodicalIF":2.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10544143","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 CYP3A5 genotype on de-novo LCP tacrolimus dosing and monitoring in kidney transplantation.","authors":"Nikhil Rao,&nbsp;Taylor Carcella,&nbsp;Neha Patel,&nbsp;Felicia Bartlett,&nbsp;Maria Aurora Posadas,&nbsp;Michael Casey,&nbsp;Derek A Dubay,&nbsp;David J Taber","doi":"10.1097/FPC.0000000000000494","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000494","url":null,"abstract":"<p><strong>Objectives: </strong>LCP tac has a recommended starting dose of 0.14 mg/kg/day in kidney transplant. The goal of this study was to assess the influence of CYP3A5 on perioperative LCP tac dosing and monitoring.</p><p><strong>Methods: </strong>This was a prospective observational cohort study of adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele).</p><p><strong>Results: </strong>In this study, 120 were screened, 90 were contacted and 52 provided consent; 50 had genotype results, and 22 patients expressed CYP3A5*1. African Americans (AA) comprised 37.5% of nonexpressors versus 81.8% of expressors (P = 0.001). Initial LCP tac dose was similar between CYP3A5 groups (0.145 vs. 0.137 mg/kg/day; P = 0.161), whereas steady state dose was higher in expressors (0.150 vs. 0.117 mg/kg/day; P = 0.026). CYP3A5*1 expressors had significantly more tac trough concentrations of less than 6 ng/ml and significantly fewer tac trough concentrations of more than 14 ng/ml. Providers were significantly more likely to under-adjust LCP tac by 10 and 20% in CYP3A5 expressors versus nonexpressors (P < 0.03). In sequential modeling, CYP3A5 genotype status explained the LCP tac dosing requirements significantly more than AA race.</p><p><strong>Conclusion: </strong>CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 3","pages":"59-65"},"PeriodicalIF":2.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9555287","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":"Pregnane X receptor gene variant rs7643645 and total mortality in subjects with nonalcoholic fatty liver disease.","authors":"Aki J Käräjämäki,&nbsp;Janne Hukkanen,&nbsp;Olavi Ukkola","doi":"10.1097/FPC.0000000000000489","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000489","url":null,"abstract":"<p><p>Pregnane X receptor (PXR) gene variants rs7643645 and rs2461823 are reported to associate with clinically and histologically more severe liver injury in nonalcoholic fatty liver disease (NAFLD). It is known that the more progressive the NAFLD, the higher the hepatic and extra-hepatic mortality and morbidity. Thus, we investigated the total mortality in Finnish middle-aged ultrasonographically verified NAFLD patients with PXR rs7643645 AA/AG ( n  = 217) or GG ( n  = 27) variants and rs2461823 CC/CT ( n  = 215) or TT ( n  = 27) variants. In up to 30 years of follow-up, PXR rs7643645 GG subjects were at an increased risk of total mortality compared with AA/AG subjects, 1.676 (1.014-2.772), P  = 0.044. The statistically significant difference prevailed after multiple adjustments for potentially confounding factors, RR, 2.024 (1.191-3.440), P  = 0.009. In the subjects without NAFLD ( n  = 731), the mortality risk was not associated with rs7643645 variants, 1.051 (0.708-1.560; P  = 0.804). There was no difference in the total mortality between the PXR rs2461823 variant subgroups, 1.141 (0.663-1.962; P  = 0.634). As the rs7643645 G variant disrupts a putative hepatocyte nuclear factor 4α binding site located in the PXR gene promoter and is associated with lower hepatic expression of PXR and its target genes, our result suggests that genetic disruption of xenobiotic metabolism increases mortality in subjects with NAFLD. Further studies are needed to confirm the results of the present study.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 2","pages":"35-39"},"PeriodicalIF":2.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226131","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":"Implementation of pharmacogenomics into inpatient general medicine.","authors":"Thomas Chen,&nbsp;Peter H O'Donnell,&nbsp;Merisa Middlestadt,&nbsp;Gregory W Ruhnke,&nbsp;Keith Danahey,&nbsp;Xander M R van Wijk,&nbsp;Anish Choksi,&nbsp;Randall Knoebel,&nbsp;Seth Hartman,&nbsp;Kiang-Teck Jerry Yeo,&nbsp;Paula N Friedman,&nbsp;Mark J Ratain,&nbsp;Edith A Nutescu,&nbsp;Kevin J O'Leary,&nbsp;Minoli A Perera,&nbsp;David O Meltzer","doi":"10.1097/FPC.0000000000000487","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000487","url":null,"abstract":"<p><p>Pharmacogenomics is a crucial piece of personalized medicine. Preemptive pharmacogenomic testing is only used sparsely in the inpatient setting and there are few models to date for fostering the adoption of pharmacogenomic treatment in the inpatient setting. We created a multi-institutional project in Chicago to enable the translation of pharmacogenomics into inpatient practice. We are reporting our implementation process and barriers we encountered with solutions. This study, 'Implementation of Point-of-Care Pharmacogenomic Decision Support Accounting for Minority Disparities', sought to implement pharmacogenomics into inpatient practice at three sites: The University of Chicago, Northwestern Memorial Hospital, and the University of Illinois at Chicago. This study involved enrolling African American adult patients for preemptive genotyping across a panel of actionable germline variants predicting drug response or toxicity risk. We report our approach to implementation and the barriers we encountered engaging hospitalists and general medical providers in the inpatient pharmacogenomic intervention. Our strategies included: a streamlined delivery system for pharmacogenomic information, attendance at hospital medicine section meetings, use of physician and pharmacist champions, focus on hospitalists' care and optimizing system function to fit their workflow, hand-offs, and dealing with hospitalists turnover. Our work provides insights into strategies for the initial engagement of inpatient general medicine providers that we hope will benefit other institutions seeking to implement pharmacogenomics in the inpatient setting.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 2","pages":"19-23"},"PeriodicalIF":2.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235320","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":"A lifetime economic research of universal HLA-B*58:01 genotyping or febuxostat initiation therapy in Chinese gout patients with mild to moderate chronic kidney disease.","authors":"Yuan Hong,&nbsp;Xichuang Chen,&nbsp;Zhiping Li,&nbsp;Xiaoyan Zhang,&nbsp;Cong Zhou,&nbsp;Yan Wang,&nbsp;Guangfei Wang,&nbsp;Wei Wu,&nbsp;Danli Zhou,&nbsp;Hai Feng Li","doi":"10.1097/FPC.0000000000000488","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000488","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate Chinese long-term economic impact of universal human leukocyte antigen B (HLA-B)*58:01 genotyping-guided urate-lowering therapy or febuxostat initiation therapy for gout patients with mild to moderate chronic kidney disease (CKD) from perspective of healthcare system.</p><p><strong>Methods: </strong>A Markov model embedded in a decision tree was structured including four mutually exclusive health states (uncontrolled-on-therapy, controlled-on-therapy, uncontrolled-off-therapy, and death). Mainly based on Chinese real-world data, the incremental costs per quality-adjusted life years (QALYs) gained were evaluated from three groups (universal HLA-B*58:01 testing strategy, and no genotyping prior to allopurinol or febuxostat initiation therapy) at 25-year time horizon. All costs were adjusted to 2021 levels based on Chinese Consumer Price Index and were discounted by 5% annually. One-way and probability sensitivity analysis were performed.</p><p><strong>Results: </strong>Among these three groups, universal HLA-B*58:01 genotyping was the most cost-effective strategy in base-case analysis according to Chinese average willingness-to-pay threshold of $37 654.50 per QALY. The based incremental cost-effectiveness ratio was $31784.55 per QALY, associated with 0.046 additional QALYs and $1463.81 increment costs per patient at a 25-year time horizon compared with no genotyping prior to allopurinol initiation strategy. Sensitivity analysis showed 64.3% robustness of these results.</p><p><strong>Conclusion: </strong>From Chinese perspective of healthcare system, HLA-B*58:01 genotyping strategy was cost-effective for gout patients with mild to moderate CKD in mainland China, especially in the most developed area, such as Beijing and Shanghai. Therefore, we suggest China's health authorities choose the genotyping strategy and make different recommendations according to the differences of local conditions.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 2","pages":"24-34"},"PeriodicalIF":2.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235318","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":"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}