Pharmacogenomics and Personalized Medicine最新文献

{"title":"Pattern Recognition Molecules of Lectin Complement Pathway in Ischemic Stroke.","authors":"Gohar Tsakanova,&nbsp;Ani Stepanyan,&nbsp;Rudi Steffensen,&nbsp;Armine Soghoyan,&nbsp;Jens Christian Jensenius,&nbsp;Arsen Arakelyan","doi":"10.2147/PGPM.S326242","DOIUrl":"https://doi.org/10.2147/PGPM.S326242","url":null,"abstract":"<p><strong>Purpose: </strong>The current study aimed to investigate in an Armenian population the levels of pattern recognition molecules (PRMs) of lectin complement pathway (LCP), MBL (mannan-binding lectin) and M-ficolin in plasma in ischemic stroke (IS), and the possible association of 11 single nucleotide polymorphisms (SNPs) in <i>MBL2, FCN1</i> and <i>FCN2</i> genes.</p><p><strong>Patients and methods: </strong>A total of 122 patients with IS and 150 control subjects were included in this study. Immunofluorometric assays (TRIFMAs) and real-time polymerase chain reactions with <i>TaqMan</i> probes were conducted.</p><p><strong>Results: </strong>According to the results, the levels of M-ficolin in IS patients are significantly higher than in control subjects, and the <i>MBL2</i> rs11003125 and rs12780112 SNPs, as well as <i>MBL2</i> rs12780112*T and <i>FCN1</i> rs10120023*T minor alleles (MAs) are negatively associated with the risk of IS. Further, <i>MBL2</i> rs11003125 and rs1800450 SNPs and the carriage of their MAs, as well as <i>FCN1</i> rs2989727 SNP and the carriage of <i>FCN1</i> rs10120023*T MA significantly alter plasma MBL and M-ficolin levels in IS patients, respectively. Five common haplotypes in <i>MBL2</i> gene and three common haplotypes in <i>FCN1</i> and <i>FCN2</i> genes were revealed, among which CGTC was negatively associated with IS and decreasing MBL plasma levels in IS.</p><p><strong>Conclusion: </strong>In conclusion, we suggest that LCP PRMs are associated with the risk of developing IS, and may also participate in pathological events leading to post-ischemic brain damage. This study emphasizes the important contribution of alterations of LCP PRMs on genomic and proteomic levels to the pathomechanisms of ischemic stroke, at least in an Armenian population.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1347-1368"},"PeriodicalIF":1.9,"publicationDate":"2021-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/70/pgpm-14-1347.PMC8544564.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39566897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H/ACA snoRNP Gene Family as Diagnostic and Prognostic Biomarkers for Hepatocellular Carcinoma.","authors":"Mi Zhang,&nbsp;Wei Zhao,&nbsp;Shanshan Liu,&nbsp;Haichuan Liu,&nbsp;Liang Liu,&nbsp;Qiling Peng,&nbsp;Chengyou Du,&nbsp;Ning Jiang","doi":"10.2147/PGPM.S333838","DOIUrl":"https://doi.org/10.2147/PGPM.S333838","url":null,"abstract":"Background The H/ACA small nucleolar ribonucleoprotein (snoRNP) gene family, including GAR1 ribonucleoprotein (GAR1), NHP2 ribonucleoprotein (NHP2), NOP10 ribonucleoprotein (NOP10), and dyskerin pseudouridine synthase 1 (DKC1), play important roles in ribosome biogenesis. However, the potential clinical value of the H/ACA snoRNP gene family in hepatocellular carcinoma (HCC) has not yet been reported. Methods Bioinformation databases were used to analyze the expression and roles of the H/ACA snoRNP gene family in HCC. Survival analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment pathway (KEGG) analyses were performed using R software. Tumor Immune Estimation Resource (TIMER) was used to analyze the correlation between the expression of the H/ACA snoRNP gene family and immune infiltration in HCC. Finally, immunohistochemistry and Western blotting were performed to verify the protein expression of the H/ACA snoRNP gene family in HCC tissues and adjacent tissues. Results The expression of the H/ACA snoRNP gene family was significantly increased in HCC samples compared to normal tissues, and the area under the curve (AUC) of GAR1, NHP2, NOP10, and DKC1 was 0.898, 0.962, 0.884, and 0.911, respectively. Increased expression of the H/ACA snoRNP gene family was associated with poor prognosis in HCC patients (Hazard Ratio, HR = 1.44 [1.02–2.04], 1.70 [1.20–2.40], 1.53 [1.09–2.17], and 1.43 [1.02–2.03], respectively; log-rank P = 0.036, 0.003, 0.014, 0.039, respectively). GO and KEGG analyses showed that co-expressed genes were primarily enriched in ribosome biogenesis. In addition, upregulated expression of H/ACA snoRNP gene family was related to the infiltration of various immune cells and multiple T cell exhaustion markers in HCC patients. Immunohistochemical analysis and Western blotting showed that the protein expression of H/ACA snoRNP gene family was higher in HCC tissues than in adjacent tissues of clinical samples. Conclusion H/ACA snoRNP gene family expression was higher in HCC tissues than in normal or adjacent tissues and was highly associated with poor prognosis of HCC patients and, therefore, has the potential to serve as diagnostic and prognostic biomarkers for HCC.","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1331-1345"},"PeriodicalIF":1.9,"publicationDate":"2021-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/d1/pgpm-14-1331.PMC8541795.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39562014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Tenofovir Alafenamide Fumarate and Tenofovir in the Chinese People: Effects of Non-Genetic Factors and Genetic Variations.","authors":"Xue Li,&nbsp;Xin-Yi Tan,&nbsp;Xue-Jun Cui,&nbsp;Ming Yang,&nbsp;Chao Chen,&nbsp;Xiao-Yun Chen","doi":"10.2147/PGPM.S329690","DOIUrl":"https://doi.org/10.2147/PGPM.S329690","url":null,"abstract":"<p><strong>Background: </strong>Tenofovir alafenamide fumarate (TAF) was approved for HBV treatment in China in 2018. Despite higher antiviral efficacy and less impact on renal function and bone mineral density, the pharmacokinetic profiles of TAF are highly variable. The objectives of this study were to investigate the pharmacokinetics of TAF in the Chinese population and explore the associations between TAF and genetic polymorphisms and non-genetic factors.</p><p><strong>Patients and methods: </strong>A total of 64 healthy Chinese subjects aged 18~65 years old were planned to enroll. According to the dietary intake status, the subjects were divided into two groups (n = 32 per group). The concentrations of TAF and tenofovir were measured by HPLC-MS/MS, and the single-nucleotide polymorphisms were analyzed by MALDI-TOF MS.</p><p><strong>Results: </strong>All the enrolled participants (18-35 years) completed the clinical trial study. Similar to the results reported in other ethnic populations, the pharmacokinetic profiles of TAF and tenofovir were highly variable in the Chinese people, and the HFHC diet can significantly increase the systemic exposure of TAF. We determined both HFHC diet and rs7311358 (<i>SLCO1B3</i>) genotypes were independently associated with TAF AUC <i>_0-t</i> , while HFHC diet, age and rs3740066 (<i>ABCC2</i>) variants were predictive of t_1/2 of tenofovir (P < 0.05). The subjects with the AA genotype in rs7311358 had significantly higher TAF AUC_0-t values (1.15 times) than those with a G allele, and the t_1/2 of tenofovir in the rs3740066 TT genotype group was 1.23 times longer than that of CC genotype group. Furthermore, there was a trend of higher TAF AUC and shorter tenofovir t_1/2 for the rs2032582 (<i>ABCB1)</i> T allele and rs3742106 (<i>ABCC4</i>) CC variant, respectively, although not statistically significant in the multiple linear regression analysis.</p><p><strong>Conclusion: </strong>This study provided new evidence to suggest a critical link between both genetic and non-genetic factors and TAF pharmacokinetics in the Chinese people.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1315-1329"},"PeriodicalIF":1.9,"publicationDate":"2021-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/aa/47/pgpm-14-1315.PMC8525415.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39562013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Pore Glycoprotein 62 Genetic Variant rs9523 is Associated with Clinical Outcomes of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Adenocarcinoma Patients.","authors":"Ji Eun Park,&nbsp;Mi Jeong Hong,&nbsp;Shin Yup Lee,&nbsp;Jang Hyuck Lee,&nbsp;Jin Eun Choi,&nbsp;Hyo-Gyoung Kang,&nbsp;Sook Kyung Do,&nbsp;Ji Yun Jeong,&nbsp;Kyung Min Shin,&nbsp;Won Kee Lee,&nbsp;Sun Ha Choi,&nbsp;Yong Hoon Lee,&nbsp;Hye Won Seo,&nbsp;Seung Soo Yoo,&nbsp;Jaehee Lee,&nbsp;Seung Ick Cha,&nbsp;Chang Ho Kim,&nbsp;Jae Yong Park","doi":"10.2147/PGPM.S329055","DOIUrl":"https://doi.org/10.2147/PGPM.S329055","url":null,"abstract":"<p><strong>Introduction: </strong>Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have represented the prototype of targeted therapy in NSCLC. Patients with EGFR-mutant lung adenocarcinoma extract an extraordinary clinical benefit from EGFR-TKIs. However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual's response to TKIs. We investigated whether genetic variants in miRNA binding sites are associated with the clinical outcome of EGFR-TKIs in lung adenocarcinoma patients.</p><p><strong>Methods: </strong>One hundred SNPs at miRNA binding sites in cancer-related genes were selected for the analysis using the crosslinking, ligation and sequencing of hybrids (CLASH) and CancerGenes database. qRT-PCR and luciferase assays were conducted to evaluate the functional relevance of the SNPs.</p><p><strong>Results: </strong><i>NUP62</i> rs9523A>G were significantly associated with worse response to EGFR-TKIs, overall survival (OS), and progression-free survival (PFS). The other three SNPs (<i>DVL2</i> rs2074216G>A, <i>ARF1</i> rs11541557G>T, and <i>UHRF1</i> rs2261988C>A) were significantly associated with worse OS and PFS. The rs9523A>G was significantly associated with decreased <i>NUP62</i> expression in tumor tissues. In addition, a significantly decreased luciferase activity was noted in <i>NUP62</i> rs9523 G allele compared to A allele.</p><p><strong>Conclusion: </strong>Genetic variants in miRNA binding sites, especially <i>NUP62</i> rs9523A>G, may be useful in predicting the clinical outcomes of EGFR-mutant lung adenocarcinoma patients treated with EGFR-TKIs.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1291-1302"},"PeriodicalIF":1.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/fd/pgpm-14-1291.PMC8493114.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39502024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Very Important Pharmacogenomics Variants in the Chinese Lahu Population.","authors":"Yujing Cheng,&nbsp;Qi Li,&nbsp;Xin Yang,&nbsp;Heng Ding,&nbsp;Wanlu Chen,&nbsp;Run Dai,&nbsp;Chan Zhang","doi":"10.2147/PGPM.S324410","DOIUrl":"https://doi.org/10.2147/PGPM.S324410","url":null,"abstract":"<p><strong>Background: </strong>Genetic polymorphism, obviously, has a potential clinical role in determining differences in drug efficacy; however, there are no reports about the pharmacogenomic information of the Lahu population. Therefore, our research aimed to screen the genotypic frequencies of the very important pharmacogenomics (VIP) mutations and determined the differences between Lahu and the other 11 populations.</p><p><strong>Methods: </strong>Agena MassARRAY (AgenaMassARRAY) single nucleotide polymorphism (SNP) genotyping technique was used to detect 81 VIP mutations of pharmacogenomics genes in Lahu, and their genotypic frequencies were compared with the other major 11 populations. Chi-square tests were used to identify different loci among these populations. Finally, the genetic structure and pairwise Fst values of Lahu and the other 11 populations were analyzed.</p><p><strong>Results: </strong>We found that the distribution of allele frequencies within different pharmacogenes in Lahu showed significantly different with other populations. Additionally, the pairwise F-statistics (Fst) values and genetic structure revealed the variants in the Lahu population as well were mostly related to the Han Chinese in Beijing, China (CHB) and the Japanese population in Tokyo, Japan (JPT) genetically.</p><p><strong>Conclusion: </strong>This study will provide a theoretical basis for safe drug use and help to establish the appropriate individualized treatment strategies in the Lahu population.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1275-1289"},"PeriodicalIF":1.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/6f/pgpm-14-1275.PMC8493477.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39502021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical Significance of miR-21 in Guiding Chemotherapy for Patients with Osteosarcoma.","authors":"Li-Zhi Li,&nbsp;Zhuang-Zhuang Wu,&nbsp;Zhi Lv","doi":"10.2147/PGPM.S321637","DOIUrl":"https://doi.org/10.2147/PGPM.S321637","url":null,"abstract":"<p><strong>Objective: </strong>The present study aims to explore the correlation between osteosarcoma (OS) chemosensitivity and the expression levels of serum and tumor tissue micro-ribonucleic acid-21 (miR-21).</p><p><strong>Methods: </strong>The relevant miR-21 expression levels in 30 patients with OS were detected, and the gender, age, tumor location, pathological type, Enneking stage, and miR-21 expression changes before and after chemotherapy were retrospectively analyzed.</p><p><strong>Results: </strong>Serum and tumor tissue miR21 expression levels were significantly higher in patients with OS than in control subjects; the serum miR-21 expressions before and after chemotherapy were not related to patient age and gender. The effective chemotherapy group showed significant differences in miR-21 expression levels before and after chemotherapy.</p><p><strong>Conclusion: </strong>Serum and tumor tissue miR-21 expression levels in patients with OS are closely related to the effects of chemotherapy, making miR-21 a potential biomarker and therapeutic target for the diagnosis and evaluation of chemotherapy effects on patients with OS.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1247-1261"},"PeriodicalIF":1.9,"publicationDate":"2021-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/b1/pgpm-14-1247.PMC8488037.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39492318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-7, miR-10a and miR-143 Expression May Predict Response to Bevacizumab Plus Chemotherapy in Patients with Metastatic Colorectal Cancer.","authors":"Alicia Romero-Lorca,&nbsp;Apolonia Novillo,&nbsp;María Gaibar,&nbsp;María Fuencisla Gilsanz,&nbsp;Miguel Galán,&nbsp;Laura Beltrán,&nbsp;Beatriz Antón,&nbsp;Diego Malón,&nbsp;Amalia Moreno,&nbsp;Ana Fernández-Santander","doi":"10.2147/PGPM.S313594","DOIUrl":"https://doi.org/10.2147/PGPM.S313594","url":null,"abstract":"<p><strong>Purpose: </strong>Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor A. It is currently used in combination with chemotherapy to treat metastatic colorectal cancer. This therapy is not equally effective in every patient; in some, mechanisms of resistance arise that remain poorly understood. The aim of the present work was to determine whether the expression of 26 miRNAs could be associated with the effectiveness of bevacizumab plus chemotherapy, with progression-free survival (PFS), and with overall survival (OS) in metastatic colorectal cancer.</p><p><strong>Patients and methods: </strong>Paraffin-embedded biopsies from 76 patients with metastatic colorectal cancer were collected to isolate miRNAs. The expression of 26 miRNAs was analyzed by quantitative RT-PCR. For the purpose of analysis, patients were classified as either \"responders\" (PFS ≥6 months since beginning treatment) or \"non-responders\" (PFS <6 months). For the analysis of PFS and OS, patients were classified into two groups using the median gene expression value as the cut-off point (\"high\" [≥50% percentile] or \"low\" [<50% percentile]). Time-to-event data were analyzed using the Kaplan-Meier method and compared by the log rank test. Cox regression was used to estimate hazard ratios (HR) and their 95% confidence intervals.</p><p><strong>Results: </strong>miR-7-5p and miR-10a-5p were more strongly expressed in non-responders than responders (p=0.049 and p=0.043, respectively), and OS was poorer in patients showing these higher expression levels (HR=2.54, 95% CI 1.42-4.55, p=0. 001, and HR=1.81, 95% CI 1.02-3.20, p=0.039, respectively). The overexpression of miR-143-3p, however, was associated with a better prognosis and significantly better PFS (HR=0.57; 95% CI: 0.33-0.96; p=0.033).</p><p><strong>Conclusion: </strong>High expression values for miR-7-5p and miR-10a-5p might be considered markers of a poorer prognosis in patients with metastatic colorectal cancer treated with bevacizumab plus chemotherapy, while the same for miR-143-3p might be a marker of better outcomes.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1263-1273"},"PeriodicalIF":1.9,"publicationDate":"2021-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ec/3c/pgpm-14-1263.PMC8488031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39491208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FTO Gene Polymorphisms Contribute to the Predisposition and Radiotherapy Efficiency of Nasopharyngeal Carcinoma.","authors":"Feng Xiao,&nbsp;Jianrong Zhou","doi":"10.2147/PGPM.S325895","DOIUrl":"https://doi.org/10.2147/PGPM.S325895","url":null,"abstract":"<p><strong>Background: </strong>Nasopharyngeal carcinoma (NPC) is mainly concentrated in East and Southeast Asia. This study aims to elucidate the potential associations of functional SNPs in the fat mass and obesity associated gene (FTO) with NPC risk and radiotherapy outcomes in a Chinese population.</p><p><strong>Methods: </strong>Functional SNP rs1477196 G>A, rs9939609 T>A, rs7206790 C>G, and rs8047395 A>G were genotyped and evaluated for their associations with NPC risk and radiotherapy outcomes.</p><p><strong>Results: </strong>Both rs9939609 (allele A versus allele T: OR=1.59; 95% CI=1.17-2.17; <i>P</i>-value=0.003) and rs8047395 (allele G versus allele A: OR=0.76; 95% CI=0.64-0.9; <i>P</i>-value=0.002) were significantly associated with risk of NPC. GTEx showed risk allele A of rs9939609 and rs8047395 were significantly associated with higher FTO mRNA levels in skeletal muscle tissue, which also corroborated our findings. Meanwhile, both rs1477196 (allele A versus allele G: OR=1.64; 95% CI=1.09-2.49; <i>P</i>-value=0.019) and rs9939609 (allele A versus allele T: OR=0.61; 95% CI=0.43-0.87; <i>P</i>-value=0.006) were significantly associated with complete remission (CR) of NPC.</p><p><strong>Conclusion: </strong>Our study identified that FTO polymorphisms contributed to the susceptibility and radiotherapy efficacy of NPC. These results shed light on the potential of establishing markers for predicting risk and personalized treatment of NPC.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1239-1245"},"PeriodicalIF":1.9,"publicationDate":"2021-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39487688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influential Factors and Efficacy Analysis of Tacrolimus Concentration After Allogeneic Hematopoietic Stem Cell Transplantation in Children with β-Thalassemia Major.","authors":"Chengxin Li,&nbsp;Jiejiu Lu,&nbsp;Siru Zhou,&nbsp;Yinyi Wei,&nbsp;Chunle Lv,&nbsp;Taotao Liu,&nbsp;Yun Wu,&nbsp;Dongni Wu,&nbsp;Jianying Qi,&nbsp;Rongda Cai","doi":"10.2147/PGPM.S325103","DOIUrl":"https://doi.org/10.2147/PGPM.S325103","url":null,"abstract":"<p><strong>Purpose: </strong>To analyze factors influencing tacrolimus (TAC) trough concentration (C₀) in β-thalassemia major (β-TM) pediatric patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and to investigate the effects of genotype polymorphism and drug-drug interactions on TAC trough concentration in children with β-TM. Furthermore, to analyze the correlation between TAC C₀ and efficacy and adverse reactions.</p><p><strong>Patients and methods: </strong>Prospectively collection of demographic information and details of combined treatment of patients with β-TM receiving HSCT, and genotypes of CYP3A4, CYP3A5, and ABCB1 (rs1045642, rs1128503, rs2032582) were obtained for each patient. Univariate analysis and multiple linear regression analysis were used to investigate influencing factors on TAC C₀. The impact of different genotypes and the co-administration of azole antifungal drugs on β-TM patients receiving TAC were evaluated, together with the correlation between acute graft-versus-host disease (aGVHD), infection, and liver injury of TAC C₀.</p><p><strong>Results: </strong>A total of 46 patients with 587 concentration data were included. The multiple linear regression results showed that the patient's sex, weight, postoperative time, hemoglobin, platelet count, serum cystatin C, and combined voriconazole were independent influencing factors of the infusion trough concentration/daily dose, C₀/D_iv. Age, body surface area, postoperative time, co-administration of voriconazole, and CYP3A4*18B are independent influencing factors of C₀/D_po. Group comparisons showed that voriconazole can affect TAC C₀ administered intravenously (IV) and orally in β-TM pediatric patients, while patient genotype can affect TAC C₀ during oral administration. TAC C₀ does not correlate with aGVHD or liver injury, but infection may be associated with TAC C₀.</p><p><strong>Conclusion: </strong>The concentration of TAC should be closely monitored when co-administered with voriconazole. It is worth considering that the influence of genotype on the trough concentration of oral TAC and individualized drug administration warrant investigation. Finally, this study indicated that C₀ is not suitable as an indicator of the efficacy of TAC.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1221-1237"},"PeriodicalIF":1.9,"publicationDate":"2021-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/eb/pgpm-14-1221.PMC8478485.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39476358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of GWAS-Identified Risk Loci with Progression, Efficacy and Toxicity of Radiotherapy of Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy.","authors":"Qinghuan Li,&nbsp;Yi Liang,&nbsp;Zeng Liu,&nbsp;Chuanyun Yu","doi":"10.2147/PGPM.S325349","DOIUrl":"https://doi.org/10.2147/PGPM.S325349","url":null,"abstract":"Background Head and neck squamous cell carcinoma (HNSCC) ranks the sixth most common cancer worldwide. This study aims to evaluate the associations of GWAS-identified HNSCC risk loci with progression, efficacy and toxicity of radiotherapy of HNSCC treated with radiotherapy. Methods Six GWAS-identified risk loci were genotyped and evaluated. Multivariate logistic regression was used to determine the associations of these SNPs with progression, efficacy and toxicity of radiotherapy of HNSCC treated with radiotherapy. Results We found that rs259919 was significantly associated with higher TNM stage (allele A vs G: OR=1.49; 95% CI: 1.09–2.03; P=0.012), while rs3135001 was significantly associated with better efficacy of radiotherapy (allele T vs C: OR=1.80, 95% CIs=1.19–2.73, P=0.005). Both SNP rs1265081 (allele A vs C: OR=1.41, 95% CIs=1.08–1.86, P=0.012) and rs3135001 (allele T vs allele C: OR=0.53, 95% CIs=0.35–0.79, P=0.002) were significantly associated with the occurrence of grade 3–4 oral mucositis. Conclusion We identified that three GWAS-identified HNSCC risk loci were significantly associated with progression, efficacy and toxicity of radiotherapy of HNSCC. Our findings strengthen the understanding of the essential role of genetic background in the progression and therapeutic effects of HNSCC.","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1205-1210"},"PeriodicalIF":1.9,"publicationDate":"2021-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/b2/pgpm-14-1205.PMC8464356.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39469018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}