Drug metabolism and personalized therapy最新文献

{"title":"Allelic frequencies of polymorphism c.521T>C (rs4149056) favor preemptive <i>SLCO1B1</i> genotyping in Armenia.","authors":"Stefan Németh, Gernot Kriegshäuser, Hasmik Hayrapetyan, Christian Oberkanins, Tamara Sarkisian","doi":"10.1515/dmpt-2024-0018","DOIUrl":"10.1515/dmpt-2024-0018","url":null,"abstract":"<p><strong>Objectives: </strong>Statins represent an important pharmacological factor for the prevention of cardiovascular diseases but may also cause severe cases of myotoxicity. Numerous studies have described the association of the <i>SLCO1B1</i> gene variant c.521C with statin-induced myopathy across different populations. This study aimed at evaluating the usefulness of preemptive <i>SLCO1B1</i> genotyping in Armenia.</p><p><strong>Methods: </strong>A total of 202 Armenian patients referred to the Center of Medical Genetics and Primary Health Care in Yerevan for upper respiratory tract infection between January and May 2022 were included in this study. Genotyping for <i>SLCO1B1</i> c.521T>C (rs4149056) was performed using a commercially available real-time PCR assay (RealFast™).</p><p><strong>Results: </strong>In total, 3/202 (1.5 %) samples were C/C homozygotes and 52/202 (25.7 %) were T/C heterozygotes, associated with a high and increased risk for statin-induced myopathy, respectively. The <i>SLCO1B1</i> c.521C allelic frequency was 14.4 %.</p><p><strong>Conclusions: </strong>The observed allele frequency of 14.4 % for the c.521C variant is slightly lower than frequencies reported from Europe, but relatively high compared to Asian populations, suggesting that preemptive <i>SLCO1B1</i> genotyping could be a useful approach for the reduction of statin-induced adverse effects in Armenia.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"159-161"},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and pharmacogenetic features of patients with upper gastrointestinal lesions at a multidisciplinary hospital: the role of nonsteroidal anti-inflammatory drugs.","authors":"Natalia P Denisenko, Anna S Zhiryakova, Ivan V Sychev, Alexander V Kryukov, Svetlana N Tuchkova, Olga Y Vakulenko, Oleg V Averkov, Valery I Vechorko, Karin B Mirzaev, Dmitry A Sychev","doi":"10.1515/dmpt-2024-0040","DOIUrl":"10.1515/dmpt-2024-0040","url":null,"abstract":"<p><strong>Objectives: </strong>Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications, but their use can be associated with a number of adverse reactions, including upper gastrointestinal lesions. The aim of the study was to identify clinical and pharmacogenetic factors associated with upper gastrointestinal lesions, including those linked to NSAIDs, in patients at a multidisciplinary hospital.</p><p><strong>Methods: </strong>The study included 92 patients (mean age 59.4±16.5 years; 47 women), who underwent esophagogastroduodenoscopy during inpatient treatment. Patients' intake of NSAIDs and gastroprotectors during the year before hospitalization was considered. Demographic, clinical, laboratory data of patients were compared between groups, including genotyping for <i>CYP2C9*2 rs179985</i>, <i>CYP2C9*3 rs1057910</i>, <i>CYP2C8*3 rs11572080</i>, <i>CYP2C8*3 rs10509681</i>, <i>PTGS-1 rs10306135</i>, <i>PTGS-1 rs12353214</i>, and <i>PTGS-2 rs20417</i> using real-time PCR.</p><p><strong>Results: </strong>In NSAIDs⁺ patients, <i>PTGS1</i> rs10306135 AT+TT genotypes increased the chance of developing gastrointestinal complications by 5.4 times (95 % CI=1.30-22.27). In total sample, smoking (OR=3.12, 95 % CI=1.15-8.46), and alcohol intake (OR=4.09, 95 % CI=1.05-15.87) increased odds of gastrointestinal damage. In NSAIDs⁺ patients omeprazole, famotidine and both famotidine and omeprazole during the last year were as ineffective as not taking gastroprotectors; in total sample famotidine (OR=0.19, 95 % CI=0.04-0.93) and two gastroprotectors (OR=0.13, 95 % CI=0.02-0.75) reduced the chance of upper gastrointestinal lesions.</p><p><strong>Conclusions: </strong>Pharmacogenetic features of patients may significantly contribute to the development NSAIDs-induced upper gastrointestinal injuries.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"69-79"},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of <i>ABCB1</i>, <i>CYP3A4</i> and <i>CYP3A5</i> gene polymorphisms on apixaban trough concentration and bleeding risk in patients with atrial fibrillation.","authors":"Alena I Skripka, Pavel M Krupenin, Olga N Kozhanova, Anna A Kudryavtseva, Ludmila V Fedina, Kristina A Akmalova, Pavel O Bochkov, Anastasiya A Sokolova, Dmitriy A Napalkov, Dmitriy A Sychev","doi":"10.1515/dmpt-2024-0013","DOIUrl":"10.1515/dmpt-2024-0013","url":null,"abstract":"<p><strong>Objectives: </strong>Apixaban, a direct oral anticoagulant, is increasingly used worldwide for the treatment and prevention of venous thromboembolism and ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Obviously, one of the ways to enhance effectiveness and safety of drug therapy is a personalized approach to therapy, which involves pharmacogenetic and pharmacokinetic tests. The study aims to investigate the effect of <i>CYP3A4*22</i>, <i>CYP3A5*3</i> and <i>ABCB1</i> polymorphisms on the pharmacokinetics of apixaban and the risk of bleeding.</p><p><strong>Methods: </strong>A total of 84 patients were enrolled in this prospective observational study. All patients received apixaban 5 or 2.5 mg twice daily. Real-time polymerase chain reaction was used to evaluate single-nucleotide polymorphisms of the <i>ABCB1</i> gene (rs1045642 and rs4148738), <i>CYP3A4*22</i> (rs35599367) C>T, <i>CYP3A5*3</i> (rs776746) A>G. A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index.</p><p><strong>Results: </strong>The C/D ratio was higher in patients aged >80 years (F(1)=11.209, p=0.00124) and was affected by serum creatinine (>133 μmol/L, F(1)=6.7, p=0.01124). <i>ABCB1</i> (rs1045642 and rs4148738), <i>CYP3A5</i> (<i>rs776746</i>) and <i>CYP3A4</i> (rs35599367) polymorphisms did not show a correlation with C/D ratio of apixaban. Multivariate logistic regression analyses showed that none of the clinical or genetic factors predicted the fact of bleeding.</p><p><strong>Conclusions: </strong>We report no significant association between <i>ABCB1</i> gene polymorphisms (rs1045642 and rs4148738), <i>CYP3A4*22</i> (rs35599367) C>T, <i>CYP3A5*3</i> (rs776746) A>G and bleeding events on apixaban treatment. Complementing the existing criteria with pharmacogenetic and pharmacokinetics information for the patients with AF will enable further individualization of apixaban.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"89-97"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of tumor necrosis factor-<i>α rs1800629</i> and interleukin-<i>10 rs1800872</i> genetic variants on type 2 diabetes mellitus susceptibility and metabolic parameters among Jordanians.","authors":"Lana Nasrallah Mousa, Yazun Jarrar, Munir Gharaibeh, Hussam Alhawari","doi":"10.1515/dmpt-2024-0002","DOIUrl":"10.1515/dmpt-2024-0002","url":null,"abstract":"<p><strong>Objectives: </strong>Diabetes mellitus (DM) is a complex chronic illness with diverse pathogenesis and associations with health complications. Genetic factors significantly contribute to DM development, and tumor necrosis factor alpha (<i>TNF-α</i>) and interleukin-10 (<i>IL-10</i>) genes play major roles. This study aims to explore the influence of <i>TNF-α rs1800629</i> and <i>IL-10 rs1800872</i> genetic variants on T2DM development in Jordanian patients at Jordan University Hospital.</p><p><strong>Methods: </strong>One-hundred and 60 diabetic and 159 non-diabetic subjects were genotyped for <i>TNF-α rs1800629</i>. Additionally, 181 diabetic and 191 non-diabetic subjects were genotyped for <i>IL-10 rs1800872</i> using PCR-RFLP genotyping method. The demographic, lipid, and glycemic parameters of the patients were obtained from the computer records in the hospital.</p><p><strong>Results: </strong><i>TNF-α rs1800629</i> and <i>IL-10 rs1800872</i> genetic variants exhibited significant different frequencies in non-T2DM subjects and T2DM patients. The difference in <i>TNF-α rs1800629</i> genotype frequency between non-T2DM and T2DM participants was significant under the dominant model, while the <i>IL-10 rs1800872</i> genotype frequency was significant under the recessive model. A significant association (p<0.05) was observed between <i>TNF-α rs1800629</i> and total cholesterol levels, and between <i>IL-10 rs1800872</i> polymorphism and glycosylated hemoglobin (HbA_1c) and creatinine levels among T2DM patients.</p><p><strong>Conclusions: </strong><i>TNF-α rs1800629</i> and <i>IL-10 rs1800872</i> are identified as genetic risk factors for T2DM. These variants also correlate with variations in cholesterol, HbA_1c, and creatinine levels among T2DM patients. Larger clinical studies are warranted to validate these findings.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"81-87"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP2D6 inhibition by diphenhydramine leading to fatal hydrocodone overdose.","authors":"Aaron G Whitt, Saeed A Jortani","doi":"10.1515/dmpt-2023-0081","DOIUrl":"10.1515/dmpt-2023-0081","url":null,"abstract":"<p><strong>Objectives: </strong>Fatal drug overdoses often involve multiple co-intoxicants, including opioids. Hydrocodone, the most prescribed opioid for pain management, is metabolized to the active metabolite hydromorphone by hepatic CYP2D6. Inhibition of CYP2D6 by other compounds can disrupt the analgesic properties of hydrocodone and extend its half-life. Diphenhydramine is an over-the-counter cold medication and is known to inhibit CYP2D6 activity.</p><p><strong>Case presentation: </strong>A woman in her late 50s was prescribed hydrocodone/acetaminophen (Norco^® 10/325). Days before her death, she began taking diphenhydramine for cold symptoms. A post-mortem toxicology report detected the following compounds by High Performance Liquid Chromatography/Time of Flight-Mass Spectrometry (LC/TOF-MS) analysis: acetaminophen (14 μg/mL), hydrocodone (410 ng/mL), dihydrocodeine (24 ng/mL), and diphenhydramine (150 ng/mL). Hydromorphone was not detected (<2 ng/mL). All compounds were detected in therapeutic concentrations, except for hydrocodone, which was present at lethal concentrations.</p><p><strong>Conclusions: </strong>This case highlights a fatal drug-drug interaction between hydrocodone and diphenhydramine. The estimated total body burden of hydrocodone was 6- to 12-fold higher than acetaminophen, which is unexpected, as these two drugs were administered as a single formulation and have similar half-lives. Furthermore, hydromorphone was undetectable. Taken together, these findings are highly suggestive of a fatal opioid overdose precipitated by diphenhydramine.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"99-102"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of <i>ABCB1</i> genetic polymorphism on carbamazepine dose requirement among Southern Indian persons with epilepsy.","authors":"Elango Dhivya, Ramasamy Kesavan, Nair P Pradeep","doi":"10.1515/dmpt-2023-0054","DOIUrl":"10.1515/dmpt-2023-0054","url":null,"abstract":"<p><strong>Objectives: </strong>Carbamazepine (CBZ) is one of the oldest, yet first line drugs for treating epilepsy. However, there is a large inter-individual difference in requirement of maintenance dose and one third of persons treated with antiepileptic drugs (AEDs) exhibit drug resistance to therapy. One of the proposed mechanisms for the drug resistance was increased expression of efflux transporter P-glycoprotein. The pharmacogenetic studies of drug transporters (<i>ABCB1</i>) done in combination therapies of AEDs were inconclusive. Hence, we have attempted to study the impact of <i>ABCB1 3435C>T</i> genetic polymorphism and CBZ monotherapy in persons with epilepsy (PWE) from South India, which is a genetically distinct population<b>.</b> With this background, this study was aimed to determine the dose of CBZ in <i>ABCB1 3435C>T</i> genotypes and to determine the distribution of <i>ABCB1 3435C>T</i> genotypes (which codes P-glycoprotein) between responders and non-responders to CBZ therapy.</p><p><strong>Methods: </strong>A cross sectional study was conducted in 200 persons with epilepsy, who were categorised as responders and non-responders according to ILAE (international league against epilepsy) criteria. Eligible participants were enrolled from the epilepsy clinic of the neurology department and five ml of blood was collected. DNA extraction and genotyping were done by phenol-chloroform method and real time polymerase chain reaction (RT-PCR), respectively.</p><p><strong>Results: </strong>The mean maintenance dose of carbamazepine was statistically significant among different genotypes (p<0.05) of <i>ABCB1 3435C>T</i> (526 vs. 637 mg/day in CC vs. TT genotype). There was no significant association between <i>ABCB1 3435C>T</i> polymorphism (p=0.827) and CBZ resistance in PWE. Duration of disease and age of onset were found to be significant in predicting the response to CBZ therapy.</p><p><strong>Conclusions: </strong>We report that <i>ABCB1 3435C>T</i> polymorphism is significantly associated with an increase in dose requirement of CBZ in persons with epilepsy from South India.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"27-34"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leaders in pharmacogenetics: Urs Albert Meyer","authors":"F. Rodrigues-Soares, I. Fricke-Galindo, Adrián LLerena","doi":"10.1515/dmpt-2024-0016","DOIUrl":"https://doi.org/10.1515/dmpt-2024-0016","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"331 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140227772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephroprotective effect of cranberry (<i>Vaccinium oxycoccos</i>) in streptozocin-induced diabetic nephropathy in mice.","authors":"Saja Majeed Shareef, Raghad Abdulsalam Khaleel, Taif M Maryoosh","doi":"10.1515/dmpt-2023-0092","DOIUrl":"10.1515/dmpt-2023-0092","url":null,"abstract":"<p><strong>Objectives: </strong>Diabetic nephropathy is a chief reason of mortality particularly in individuals with renal dysfunction. The current research was aimed to assess the nephroprotective portion of <i>Vaccinium oxycoccos</i> toward mice diabetic nephropathy induced by streptozotocin (STZ). <i>V. oxycoccos</i> was purchased and used for hydroalcoholic extraction.</p><p><strong>Methods: </strong>Sixty male mice were subjected to STZ-intraperitoneal injection (45 mg/kg). After diabetes induction, mice were divided into five groups of diabetic control (received only STZ), non-diabetic control (received only citrate buffer), two <i>V. oxycoccos</i> treatment (received <i>V. oxycoccos</i> extract (200 and 400 mg/kg) oral daily by gavage), and metformin treatment (received metformin (500 mg/kg) oral daily by gavage). Glucose and weight of mice were checked weekly.</p><p><strong>Results: </strong>After 28 days, the effect of <i>V. oxycoccos</i> extract on serum and urine parameters were assessed. STZ caused significant decreased in the mice body weight. Mice treated with the <i>V. oxycoccos</i> (400 mg/kg) harbored the lowest weight loss at day 28 (70.2±1.38 g). STZ caused significant increase in the mice FBS. Mice treated with the <i>V. oxycoccos</i> (400 mg/kg) harbored the lowest FBS at day 28 (189.2±1.20 mg/dL). Treatment of mice with <i>V. oxycoccos</i> (400 mg/kg) caused the lowest increase in the levels of cholesterol, HbA_1c and triglycerides compared to the diabetic control mice. Compared to the diabetic control group, mice treated with <i>V. oxycoccos</i> (400 mg/kg) had the highest HDL, insulin, SOD, and GSH (p<0.05). The lowest serum BUN, CR, and UR were found in mice treated with <i>V. oxycoccos</i> (400 mg/kg). Anti-inflammatory effects of <i>V. oxycoccos</i> (400 mg/kg) was shown by the lowest TNF-α, IL-6, and TGF-β1 concentration in mice treated with <i>V. oxycoccos</i> (400 mg/kg).</p><p><strong>Conclusions: </strong>The current study disclosed that treatment with <i>V. oxycoccos</i> resulted in substantial development in the serum and urine parameters and also antioxidant and anti-inflammatory response of STZ-induced diabetic mice.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"35-45"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential of oncology biomarkers: advancements in clinical theranostics.","authors":"Ankit Kumar Dubey, Ishnoor Kaur, Reecha Madaan, Shikha Raheja, Rajni Bala, Manoj Garg, Suresh Kumar, Viney Lather, Vineet Mittal, Deepti Pandita, Rohit Gundamaraju, Rajeev K Singla, Rohit Sharma","doi":"10.1515/dmpt-2023-0056","DOIUrl":"10.1515/dmpt-2023-0056","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of \"omic\" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment.</p><p><strong>Content: </strong>In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack.</p><p><strong>Summary and outlook: </strong>We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"5-20"},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of ITPA 94C>A genetic polymorphisms with azathioprine induced adverse effects in the South Indian population.","authors":"Reka Deva, Priyadharsini Rajendran, Sivaranjini Ramasamy, Senthamizh Selvan, Kesavan Ramasamy","doi":"10.1515/dmpt-2023-0061","DOIUrl":"10.1515/dmpt-2023-0061","url":null,"abstract":"<p><strong>Objectives: </strong>Azathioprine (AZA) is an effective immunosuppressant commonly used for malignancy and immune-mediated disorders. The association between genetic polymorphisms and AZA-induced adverse effects has not been elucidated. Hence this study aimed to evaluate the relationship between single nucleotide polymorphisms of ITPA (C94A) with azathioprine-induced adverse effects.</p><p><strong>Methods: </strong>A cross-sectional study was performed on 120 patients who were on AZA therapy for immunobullous disorders and inflammatory bowel disease (IBD). Eligible patients were enrolled from outpatient Departments of dermatology and medical gastroenterology and five mL of blood was collected after obtaining written informed consent. DNA extraction and genotyping were done by phenol-chloroform method and real-time polymerase chain reaction (RT-PCR), respectively.</p><p><strong>Results: </strong>The minor allele frequency of ITPA (A allele) was 30.8 %. The mutant genotypes of ITPA (C94A) were found to have no significant association with overall adverse effects in the South Indian patients on AZA therapy.</p><p><strong>Conclusions: </strong>We report no significant association between ITPA rs1127354 genetic polymorphism and adverse effects in the South Indian patients on AZA therapy.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"21-26"},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}