Pharmacogenomics And Personalized Medicine[JOURNAL]
Sun
200 papers
Genetic Variants of Associated with Ischemic Stroke Susceptibility in the Han Population from Southern China.
Huang K, Ma T, Li Q … +7 more , Zhou Y, Qin T, Zhong Z, Tang S, Zhang W, Zhong J, Lu S
Pharmgenomics Pers Med · 2023 · PMID 37342180 · Full text
BACKGROUND: The pathophysiological mechanism of ischemic stroke is complex. Traditional risk factors cannot fully or only partially explain the occurrence and development of IS. Genetic factors are getting more and more...
BACKGROUND: The pathophysiological mechanism of ischemic stroke is complex. Traditional risk factors cannot fully or only partially explain the occurrence and development of IS. Genetic factors are getting more and more attention. Our study aimed to explore the association between gene polymorphism and susceptibility to IS. METHODS: A total of 1322 volunteers were enrolled to perform an association analysis through SNPStats online software. Using FPRP (false-positive report probability) to detect whether the result is a noteworthy finding. The interaction of SNP-SNP in IS risk was assessed by multi-factor dimensionality reduction. Statistical analysis of this study was mainly completed by SPSS 22.0 software. RESULTS: Mutant allele "A" (OR = 1.24) and genotype "AA" (OR = 1.49) or "GA" (OR = 1.26) of rs2108622 are risk genetic factors for IS. Rs2108622 is significantly associated with an increased risk of IS among subjects who are females, aging >60 years old, with BMI ≥24 kg/m, and smoking or drinking volunteers. -rs3093106 and -rs3093105 are associated with susceptibility to IS among smoking, drinking subjects, or IS patients complicated with hypertension. CONCLUSION: -rs2108622, -rs3093106, and -rs3093105 are associated with an increased risk of IS.
Exploration into Plasma Hsa_circ_0052184 as a New Biomarker of Colorectal Cancer Prognosis.
Zheng E, Xiao D
Pharmgenomics Pers Med · 2023 · PMID 37333495 · Full text
BACKGROUND: Circular RNAs (circRNAs) are strong modulators of tumor pathology. Herein, our goal was to examine the plasma hsa_circ_0052184 content among colorectal cancer (CRC) patients, and assess its association with p...
BACKGROUND: Circular RNAs (circRNAs) are strong modulators of tumor pathology. Herein, our goal was to examine the plasma hsa_circ_0052184 content among colorectal cancer (CRC) patients, and assess its association with patient clinicopathological profile and diagnostic values. METHODS: Overall, we collected 228 presurgical CRC and 146 normal plasma samples from The First People's Hospital of Wenling. Circulating hsa_circ_0052184 levels were assessed via qRT-PCR, and the diagnostic prediction was conducted with the receiver operating characteristic (ROC) curve. RESULTS: Relative to healthy controls, CRC patients exhibited markedly enhanced circulating hsa_circ_0052184 levels, which were closely correlated with advanced stage of disease and worse outcome. Based on our uni- (UA) and multivariate assessments (MA), elevated hsa_circ_0052184 levels were a stand-alone predictor of poor prognosis. The ROC curve depicted an area under the curve (AUC) for CRC diagnosis to be 0.9072. CONCLUSION: Circulating hsa_circ_0052184 is a potential bioindicator of CRC outcome.
Genetic Influence of Fracture Nonunion (FNU): A Systematic Review.
Sadat-Ali M, Al-Omar HK, AlTabash KW … +3 more , AlOmran AK, AlDakheel DA, AlSayed HN
Pharmgenomics Pers Med · 2023 · PMID 37305020 · Full text
PURPOSE: Nonunion of fractures occurs in about 15% of all fractures causing repeated surgical interference and prolonged morbidity. We performed this systematic review to assess genes and polymorphisms influencing fractu...
PURPOSE: Nonunion of fractures occurs in about 15% of all fractures causing repeated surgical interference and prolonged morbidity. We performed this systematic review to assess genes and polymorphisms influencing fractures' nonunion (FNU). METHODS: We searched between 2000 and July 2022 in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Genome Wide Association Studies (GWAS) Catalog, and the Science Citation Index, with the keywords nonunion of fractures, genetic influence, and GWAS. The exclusion criteria were review articles and correspondence. The data were retrieved to determine the number of studies, genes, and polymorphisms and the total number of subjects screened. RESULTS: A total of 79 studies were reported on nonunion of fractures and genetic influence. After the inclusion and exclusion criteria, ten studies with 4402 patients' data were analyzed. Nine studies were case-controlled, and 1 GWAS. It was identified that patients with polymorphisms in the genes are prone to develop a nonunion of fractures. CONCLUSION: We believe that for patients who develop an early nonunion of fractures, a genetic study should be conducted for single nucleotide polymorphism (SNP) and genes so that alternative and more aggressive treatment can be performed to heal fractures without prolonged morbidity.
Clinical and Gene Analysis of Fatty Acid Oxidation Disorders Found in Neonatal Tandem Mass Spectrometry Screening.
Wang X, Fang H
Pharmgenomics Pers Med · 2023 · PMID 37305019 · Full text
OBJECTIVE: To investigate the clinical and gene mutation characteristics of fatty acid oxidative metabolic diseases found in neonatal screening. METHODS: A retrospective analysis was performed on 29,948 neonatal blood ta...
OBJECTIVE: To investigate the clinical and gene mutation characteristics of fatty acid oxidative metabolic diseases found in neonatal screening. METHODS: A retrospective analysis was performed on 29,948 neonatal blood tandem mass spectrometry screening samples from January 2018 to December 2021 in our neonatal screening centre. For screening positive, recall review is still suspected of fatty acid oxidation metabolic disorders in children as soon as possible to improve the genetic metabolic disease-related gene detection package to confirm the diagnosis. All diagnosed children were followed up to the deadline. RESULTS: Among 29,948 neonates screened by tandem mass spectrometry, 14 cases of primary carnitine deficiency, six cases of short-chain acyl coenzyme A dehydrogenase deficiency, two cases of carnitine palmitoyltransferase-I deficiency and one case of multiple acyl coenzyme A dehydrogenase deficiency were recalled. Except for two cases of multiple acyl coenzyme A dehydrogenase deficiency that exhibited [manifestations], the other 21 cases were diagnosed pre-symptomatically. Eight mutations of 5 gene were detected, including c.51C>G, c.403G>A, c.506G>A, c.1400C>G, c.1085C>T, c.706C>T, c.1540G>C and c.338G>A. Compound heterozygous mutation of gene c.2201T>C, c.1318G>A, c.2246G>A, c.2125G>A and ETFA gene c.365G>A and c.699_701delGTT were detected, and new mutation sites were found. CONCLUSION: Neonatal tandem mass spectrometry screening is an effective method for identifying fatty acid oxidative metabolic diseases, but it should be combined with urine gas chromatography-mass spectrometry and gene sequencing technology. Our findings enrich the gene mutation profile of fatty acid oxidative metabolic disease and provide evidence for genetic counselling and prenatal diagnosis in families.
Leucyl and Cystinyl Aminopeptidase as a Prognostic-Related Biomarker in OV Correlating with Immune Infiltrates.
Ma Q, Chang L, Wang W … +7 more , Che L, Song X, Li G, Zhang Y, Chen Y, Gu Z, Ge X
Pharmgenomics Pers Med · 2023 · PMID 37293607 · Full text
BACKGROUND: It was indicated that tumor intrinsic heterogeneity and the tumor microenvironment (TME) of ovarian cancer (OV) influence immunotherapy efficacy and patient outcomes. Leucyl and cystinyl aminopeptidase (LNPEP...
BACKGROUND: It was indicated that tumor intrinsic heterogeneity and the tumor microenvironment (TME) of ovarian cancer (OV) influence immunotherapy efficacy and patient outcomes. Leucyl and cystinyl aminopeptidase (LNPEP) encodes a zinc-dependent aminopeptidase, which has been proved to participant in the vesicle-mediated transport and class I MHC mediated antigen processing and presentation. However, the function of LNPEP in TME of OV and its potential molecular mechanisms have not been determined. Therefore, we aimed to investigate a prognostic biomarker which may be helpful in identifying TME heterogeneity of ovarian cancer. METHODS: In this study, bioinformatics databases were used to explore the expression profile and immune infiltration of LNPEP. Bioinformatics analyses of survival data and interactors of LNPEP were conducted to predict the prognostic value of LNPEP in OV. The protein levels of LNPEP were validated by Western blot and immunohistochemistry. RESULTS: Based on the TCGA data, our data displayed that the mRNA expression of LNPEP was markedly down-regulated in ovarian cancer than that in para-cancer tissues, contrary to the protein level. Importantly, high LNPEP expression was associated with poor prognosis in patients with OV. Furthermore, Cox regression analysis showed that LNPEP was an independent prognostic factor in OV. GO and KEGG pathway analyses indicated the co-expressed genes of LNPEP were mainly related to a variety of immune-related pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, and immunoregulatory interaction. Our data also demonstrated that the expression of LNPEP was strongly correlated with immune infiltration levels, immunomodulators, chemokines and chemokine receptors. CONCLUSION: In our study, we identified and established a prognostic signature of immune-related LNPEP in OV, which will be of great value in predicting the prognosis of clinical trials and may become a new therapeutic target for immunological research and potential prognostic biomarker in OV.
Exploring the Correlation Between , a Potential Target Gene of Gastric Cancer, and Immune Cell Infiltration.
Gu X, Shen H, Xiang Z … +5 more , Li X, Zhang Y, Zhang R, Su F, Wang Z
Pharmgenomics Pers Med · 2023 · PMID 37284492 · Full text
INTRODUCTION: , an orphan G protein-coupled receptor (GPCR), is essential for the progression of gastrointestinal cancers. However, it is still unclear how affects tumor immunity and patient prognosis in gastric cancer...
INTRODUCTION: , an orphan G protein-coupled receptor (GPCR), is essential for the progression of gastrointestinal cancers. However, it is still unclear how affects tumor immunity and patient prognosis in gastric cancer (GC). METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were searched in this investigation to assess the expression patterns of in GC tissues and normal gastric mucosa. The findings were further verified using immunohistochemical tests and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method, univariate logistic regression, and Cox regression were then used to investigate the relationship between and clinical traits. Additionally, the potential correlation between , immune checkpoint genes, and immune cell infiltration levels was investigated. RESULTS: As per the research findings, GC tissues had higher levels of than normal tissues. Additionally, individuals with high expression of had a worse 10-year overall survival (OS), in contrast with those having a low expression of ( < 0.001). The OS of GC can be predicted using a validated nomogram model. The expression of demonstrated a negative correlation with CD8+ T cells. When compared to the low-expression group of , Tumor Immune Dysfunction and Exclusion (TIDE) analysis demonstrated that the high-expression group had a considerably higher risk of immune evasion. A remarkable difference (variation) was observed in the levels of expression across both groups, ie, low and high-risk groups, as determined by the immune phenomenon scores (IPS) immunotherapy assessment. CONCLUSION: By examining from various biological perspectives, it was determined that can act as a predictive biomarker for poor patient prognosis in GC. Additionally, it was observed that is capable of suppressing the proliferation of CD8+ T cells and facilitating immune evasion.
Serum Osteopontin, KL-6, and Syndecan-4 as Potential Biomarkers in the Diagnosis of Coal Workers' Pneumoconiosis: A Case-Control Study.
Hou Z, Zhang X, Gao Y … +4 more , Geng J, Jiang Y, Dai H, Wang C
Pharmgenomics Pers Med · 2023 · PMID 37284491 · Full text
BACKGROUND: Coal worker's pneumoconiosis (CWP) is a chronic occupational disease mainly caused by coal dust inhalation in miners. This study aimed to investigate the clinical value of Osteopontin (OPN), KL-6, Syndecan-4...
BACKGROUND: Coal worker's pneumoconiosis (CWP) is a chronic occupational disease mainly caused by coal dust inhalation in miners. This study aimed to investigate the clinical value of Osteopontin (OPN), KL-6, Syndecan-4 and Gremlin-1 as serum biomarkers in CWP. PATIENTS AND METHODS: We integrated reported lung tissues transcriptome data in pneumoconiosis patients with silica-exposed alveolar macrophage microarray data to identify four CWP-associated serum biomarkers. The serum concentrations of Osteopontin, Krebs von den Lungen-6 (KL-6), Syndecan-4 and Gremlin-1 were measured in 100 healthy controls (HCs), 100 dust-exposed workers (DEWs) and 200 patients of CWP. Receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity, specificity, cut-off value and area under the curve (AUC) value of biomarkers. RESULTS: The pulmonary function parameters decreased sequentially, and the serum OPN, KL-6, Syndecan-4 and Gremlin-1 concentrations were increased sequentially among the HC, DEW and CWP groups. Among all participants, multivariable analysis revealed that these four biomarkers were negatively correlated with the pulmonary function parameters (all <0.05). Compared with HCs, patients with higher OPN, KL-6, Syndecan-4 and Gremlin-1 had higher risk for CWP. The combination of OPN, KL-6, and Syndecan-4 can improve the diagnostic sensitivity and specificity of CWP patients differentiated from HCs or DEWs. CONCLUSION: OPN, KL-6 and Syndecan-4 are novel biomarkers that can be used for CWP auxiliary diagnosis. The combination of three biomarkers can improve the diagnostic values of CWP.
Mental Health Prescribers' Perceptions on the Use of Pharmacogenetic Testing in the Management of Depression in the Middle East and North Africa Region.
Aboelbaha S, Zolezzi M, Abdallah O … +1 more , Eltorki Y
Pharmgenomics Pers Med · 2023 · PMID 37274729 · Full text
OBJECTIVE: A wide variety of commercial pharmacogenetic (PGx) tools are available worldwide to guide treatment selection for depression based on individuals' genetic profiles. However, the use of genetic testing to infor...
OBJECTIVE: A wide variety of commercial pharmacogenetic (PGx) tools are available worldwide to guide treatment selection for depression based on individuals' genetic profiles. However, the use of genetic testing to inform psychiatric care has faced challenges due to the limited training and education for mental health clinicians. The aim of this study was to explore the knowledge, level of engagement, and perspectives on the use of PGx testing when making depression management decisions among practicing psychiatrists within the Middle East and North Africa (MENA) region. METHODS: This is a qualitative study using semi-structured interviews. Consenting psychiatrists were interviewed through an online platform (Skype or Microsoft Teams). Interviews were audio recorded, transcribed, and thematically analyzed with the assistance of NVivo software. RESULTS: Eighteen interviews from 12 countries have been conducted. Analysis of the current interviews produced five major themes including: (1) Overall perceptions and attitudes; (2) Knowledge and awareness; (3) Education, training, and professional experience; (4) Facilitators and barriers; and (5) Ethical dilemmas. These themes support the notion that there is limited, mostly basic, education, knowledge, and training regarding genetic testing in the management of depression, although there is significant interest and willingness in the part of prescribers to adopt this strategy in their practice. CONCLUSION: The findings of the study suggest that psychiatrists practicing in the MENA region appear to be interested in implementing PGx testing when managing people with depression. However, it is also important to recognize that this cannot be achieved unless more supporting strategies are implemented within their current health system environment.
Role of Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population.
Huang K, Ma T, Li Q … +7 more , Zhong Z, Qin T, Zhou Y, Zhang W, Tang S, Zhong J, Lu S
Pharmgenomics Pers Med · 2023 · PMID 37274728 · Full text
INTRODUCTION: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of single nucleotide polymorphisms (SNPs) in IS in the Chinese popu...
INTRODUCTION: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of single nucleotide polymorphisms (SNPs) in IS in the Chinese population. METHODS: 1302 subjects (651 controls and 651 cases) were recruited in this case-control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of were selected by the 1000 genomes project database. The association between SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk. RESULTS: In the research, loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24. CONCLUSION: The study revealed that there is a significant association between loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.
Plasma Homocysteine (Hcy) Concentration Functions as a Predictive Biomarker of SPECT-Evaluated Post-Ischemic Hyperperfusion in Acute Ischemic Stroke.
Wang Y, Hou R, Liu Y
Pharmgenomics Pers Med · 2023 · PMID 37256202 · Full text
INTRODUCTION: Homocysteine (Hcy) concentration has been reported to be associated with ischemic stroke. In this study, we aimed to investigate the potential of plasma Hcy in the prediction of post-ischemic hyperperfusion...
INTRODUCTION: Homocysteine (Hcy) concentration has been reported to be associated with ischemic stroke. In this study, we aimed to investigate the potential of plasma Hcy in the prediction of post-ischemic hyperperfusion in AIS patients, which was diagnosed with the single-photon emission computed tomography (SPECT) method. METHODS: A total of 112 ischemic stroke patients were recruited in this study. According to whether the patients were subjected to post-ischemic hyperperfusion, all recruited subjects were divided into a post-ischemic hyperperfusion (+) group (N=48) and post-ischemic hyperperfusion (-) group (N=64). The basic demographical data, clinicopathological data and laboratory biochemical data were collected and compared. Level of homocysteine (Hcy) and cystatin-C (Cys-C) and their potential as predictive biomarker are also investigated. RESULTS: No significant differences were spotted between the post-ischemic hyperperfusion group (+) and post-ischemic hyperperfusion (-) group in respect to the basic demographical and clinicopathological data. And the serum Hcy levels were lower in the post-ischemic hyperperfusion (+) group. Moreover, ROC analysis indicated significant relationships between Hcy levels and the onset of post-ischemic hyperperfusion. CONCLUSION: In conclusion, we validated that the plasma Hcy concentration can be used as a predictive biomarker of SPECT-evaluated post-ischemic hyperperfusion in patients suffering from acute ischemic stroke.
Exploration and Validation of Pancreatic Cancer Hub Genes Based on Weighted Gene Co-Expression Network Analysis and Immune Infiltration Score Analysis.
Li XX, Li H, Jin LQ … +1 more , Tan YB
Pharmgenomics Pers Med · 2023 · PMID 37252337 · Full text
OBJECTIVE: To find pancreatic cancer (PC)-related hub genes based on weighted gene co-expression network analysis (WGCNA) construction and immune infiltration score analysis and validate them immunohistochemically by cli...
OBJECTIVE: To find pancreatic cancer (PC)-related hub genes based on weighted gene co-expression network analysis (WGCNA) construction and immune infiltration score analysis and validate them immunohistochemically by clinical cases, to generate new concepts or therapeutic targets for the early diagnosis and treatment of PC. MATERIAL AND METHODS: In this study, WGCNA and immune infiltration score were utilized to identify the relevant core modules of PC and the hub genes within these core modules. RESULTS: Using WGCNA analysis, data from PC and normal pancreas integrated with TCGA and GTEX were analyzed and brown modules were chosen from the six modules. Five hub genes, including DPYD, FXYD6, MAP6, FAM110B, and ANK2, were discovered to have differential survival significance via validation tests utilizing survival analysis curves and the GEPIA database. The DPYD gene was the only gene associated with PC survival side effects. Validation of the Human Protein Atlas (HPA) database and immunohistochemical testing of clinical samples showed positive results for DPYD expression in PC. CONCLUSION: In this study, we identified DPYD, FXYD6, MAP6, FAM110B, and ANK2, as immune-related candidate markers for PC. Only the DPYD gene had a negative impact on the survival of PC patients. Through validation of the HPA database and immunohistochemical testing of clinical cases, we believe that the DPYD gene brings novel ideas and therapeutic targets in the diagnosis and treatment of PC.
Giant Multilocular-Cystic Metaplastic Thymoma: A Case Report.
Han L, Gao B, Wang EH … +1 more , Wang L
Pharmgenomics Pers Med · 2023 · PMID 37229516 · Full text
The metaplastic thymoma with giant multilocular-cyst formation had not been documented. The metaplastic thymoma is an extremely rare primary thymic epithelial tumor with an indolent clinical course. It is characterized b...
The metaplastic thymoma with giant multilocular-cyst formation had not been documented. The metaplastic thymoma is an extremely rare primary thymic epithelial tumor with an indolent clinical course. It is characterized by a histologic biphasic appearance, which is consisted of solid epithelial areas and spindle cells as the background. This specific pattern can be easily mistaken as the type A thymoma or the type A components of type AB thymoma. When cystic change occurs in metaplastic thymoma, it will bring more challenges for both imaging and pathological diagnosis. Herein, we reported an extremely rare case of a 14.9-cm giant tumor located in the anterior mediastinum of an elderly female. The tumor is consisted of both multilocular cysts and solid components, with the largest cyst measuring 6 cm in diameter. The multilocular cyst contained hemorrhage, calcification, and cholesterol crystal cracks without cell lining. In the solid area, the epithelial cell nests were surrounded by spindle cells with scattered lymphocytes. With immunostains, neither type of cells was CD20 positive. The epithelial cells were positive for CK and P63, while the spindle cells expressed vimentin and EMA. Fluorescence in situ hybridization analysis revealed that the tumor harbored gene fusions. Accordingly, although the multilocular cystic pattern set a diagnostic challenge, the diagnosis of metaplastic thymoma was rendered due to the immunohistochemistry staining and gene rearrangement detection.
The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review.
Marwa KJ, Kapesa A, Kamugisha E … +1 more , Swedberg G
Pharmgenomics Pers Med · 2023 · PMID 37223718 · Full text
BACKGROUND: Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major sourc...
BACKGROUND: Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations. METHODS: Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies. RESULTS: Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles. CONCLUSION: This review reports lack of influence of CYP3A4*1B, CYP3A5*3, CYP2C8*3 and CYP2B6*6 SNPs on PK profiles, efficacy and safety in SSA among malaria patients.
Case Report: A Novel Homozygous Mutation of Cyclin O Gene Mutation in Primary Ciliary Dyskinesia with Short Stature.
Gong D, Tang Q, Yan LJ … +5 more , Ye XM, Yang YC, Zou L, Ji Q, Wen XL
Pharmgenomics Pers Med · 2023 · PMID 37220549 · Full text
BACKGROUND: Primary ciliary dyskinesia (PCD) is a group of autosomal recessive genetic diseases caused by abnormal ciliary ultrastructure and/or function, resulting in reduced ciliary clearance function or other dysfunct...
BACKGROUND: Primary ciliary dyskinesia (PCD) is a group of autosomal recessive genetic diseases caused by abnormal ciliary ultrastructure and/or function, resulting in reduced ciliary clearance function or other dysfunctions. PCD is one of the causes of recurrent respiratory tract infections in children. At present, there is no gold standard for diagnosis. In patients clinically suspected with PCD, a variety of examination methods are available to assist in diagnosis, such as high-speed video microscopic imaging to analyze ciliary movement patterns, transmission electron microscopy to observe ciliary ultrastructure, genetic testing, and detection of nitric oxide content in nasal expiratory air. CASE DESCRIPTION: We present a case summary of the clinical data and treatment process of a child with PCD and short stature induced by Novel exon 1 of CCNO mutation (NM-021147.5) at c.323del, and the proband father and mother were heterozygous mutators, who was diagnosed and treated in the Pediatric Healthcare Department of our hospital. We treated the child with recombinant human growth hormone to increase the height, and the patient was also advised to improve nutrition, prevent and control infections, and encouraged sputum expectoration. We also recommended regular follow-up visits to the outpatient department, and to seek other symptomatic and supportive treatments as necessary. CONCLUSION: The height and nutritional status of the child improved after treatment. We also reviewed relevant literature to help clinicians improve their understanding of this disease.
Clinical Knowledge, Attitude, and Perceptions of Community Pharmacists Towards Pharmacogenomics - A Cross-Sectional Study from Saudi Arabia.
Alrabiah Z, Syed W, Babelghaith SD … +1 more , Al Arifi MN
Pharmgenomics Pers Med · 2023 · PMID 37187880 · Full text
BACKGROUND AND AIMS: It is crucial to provide healthcare personnel with the necessary knowledge and understanding of genetic testing and pharmacogenomics. The purpose of this study is to assess the knowledge, attitudes,...
BACKGROUND AND AIMS: It is crucial to provide healthcare personnel with the necessary knowledge and understanding of genetic testing and pharmacogenomics. The purpose of this study is to assess the knowledge, attitudes, views, and considerations of Community pharmacists (CPs) about pharmacogenomics and genetics. METHODS AND MATERIALS: A cross-sectional web-based study was conducted among practicing pharmacists Between January and February of 2022. Participants were recruited through a convenient sampling technique. A total of 23 item questionnaires were used to assess the Knowledge Attitudes, Views, and Considerations toward Pharmacogenomics among pharmacists. RESULTS: The mean age of the CPs were 28.45±7.29(Std). Among the CPs, 38.4% (98 of 255) of them were correctly identified human chromosomes, and the majority of them 73.3% knew that adverse reactions can be caused by genetic changes in the human body. A total of 194 CPs agreed that certain drugs can be affected by genetic changes in the patient. In this study, one-third (33%) of the CPs were found to have good knowledge, while most (66.3%) of the CPs were found poor knowledge of pharmacogenomics and genetics. Furthermore, the knowledge score is significantly different concerning the qualification of the CPs (=0.0001). CONCLUSION: The current findings, demonstrated a majority of the CPs found a lack of knowledge and understanding regarding pharmacogenomics and its perspectives, there is a need to increase awareness among CPs to reduce the knowledge gap of pharmacogenomics and genetics.
A Preliminary Study on the Correlation Between Age and Endometrial Receptivity.
Guo S, Zhang D, Zhao S … +3 more , Zhang H, Sun Y, Yan L
Pharmgenomics Pers Med · 2023 · PMID 37180957 · Full text
BACKGROUND: It is well established that female fertility declines with age, primarily because of loss of ovarian function. However, few studies have clarified the relationship between increasing age and endometrial recep...
BACKGROUND: It is well established that female fertility declines with age, primarily because of loss of ovarian function. However, few studies have clarified the relationship between increasing age and endometrial receptivity. Here, we aimed to study the impact of age on endometrial receptivity, meanwhile, we examined the expression of endometrial mesenchymal stem cell (eMSC) surface markers (CD146 and PDGF-Rβ), essential for endometrial development and re-growth, in different age groups. METHODS: Participants were enrolled in this study between October 2020 and July 2021. All 31 patients were divided into three age groups; early (30-39 years old, n=10), intermediate (40-49 years old, n=12) and advanced (≥50 years old, n=9). We assessed localization and expression of CD146 and PDGF-Rβ by immunofluorescence and further analyzed selected endometrial receptivity markers (Homeobox A10 HOXA10, leukemia inhibitory factor LIF and osteopontin) and steroid hormone receptors by immunohistochemistry. RESULTS: There were no significant differences in expression of HOXA10 and OPN (p>0.05) among the three groups. However, we found a significant difference in LIF expression between the early and advanced age groups, with higher expression noted in the latter group (p=0.02). Similarly, estrogen receptor (ER) and progesterone receptor (PR) expression were significantly increased (p=0.01 and p=0.01, respectively) in the advanced age group compared with the early age group. There were no significant difference in CD146 and PDGF-Rβ expression among the three groups (p>0.05). CONCLUSION: These results suggest that the age of the patient does not influence their endometrial receptivity. So, this study serves to increase our understanding of the impact of age and eMSCs on endometrial receptivity and expands the etiology of age-related infertility.
MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis.
Zhang Q, Fu P, Cao Z … +6 more , Huang H, Wen Q, Wang K, Kong T, Wu X, Zheng J
Pharmgenomics Pers Med · 2023 · PMID 37159804 · Full text
PURPOSE: Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relatio...
PURPOSE: Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms. PATIENTS AND METHODS: In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy. RESULTS: The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups. CONCLUSION: Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.
Genetic Variations are Associated with Ventricular Septal Defect in the Chinese Tibetan Population Through Whole-Exome Sequencing.
Zhang X, Zhen D, Li X … +8 more , Yi F, Zhang Z, Yang W, Li X, Sheng Y, Liu X, Jin T, He Y
Pharmgenomics Pers Med · 2023 · PMID 37138656 · Full text
BACKGROUND: Ventricular septal defect (VSD) is the most common congenital cardiac abnormality in children and the second most common in adults. This study aimed to explore the potentially causative genes in VSD patients...
BACKGROUND: Ventricular septal defect (VSD) is the most common congenital cardiac abnormality in children and the second most common in adults. This study aimed to explore the potentially causative genes in VSD patients in the Chinese Tibetan population, and to provide a theoretical basis for the genetic mechanism of VSD. METHODS: Peripheral venous blood was collected from 20 VSD subjects, and whole-genome DNA was extracted. High-throughput sequencing was performed on qualified DNA samples using whole-exome sequencing (WES) technology. After filtering, detecting, and annotating qualified data, single nucleotide variations (SNVs) and insertion-deletion (InDel) markers were analyzed, and data processing software such as GATK, SIFT, Polyphen, and MutationTaster were used for comparative evaluation and prediction of pathogenic deleterious variants associated with VSD. RESULTS: A total of 4793 variant loci, including 4168 SNVs, 557 InDels and 68 unknown loci and 2566 variant genes were obtained from 20 VSD subjects through bioinformatics analysis. According to the screening of the prediction software and database, the occurrence of VSD was predicted to be associated with five inherited pathogenic gene mutations, all of which were missense mutations, including (c.1396C >A:p.Gln466Lys), (c.235C >T:p.Arg79Cys), (c.629G >A:p.Arg210Gln), (c.1138G >A:p.Gly380Arg), (c.1363C >T:p.Arg455Trp). CONCLUSION: This study demonstrated that gene variants were potentially associated with VSD in Chinese Tibetan population.
Acute Myeloid Leukemia Secondary to Chronic Lymphocytic Leukemia After Prolonged Chlorambucil Therapy: A Case Report.
Wu Y, Liu S, Wang D … +1 more , Yao X
Pharmgenomics Pers Med · 2023 · PMID 37138655 · Full text
BACKGROUND: This study aimed to improve the understanding of acute myeloid leukemia (AML) secondary to chronic lymphocytic leukemia (CLL), and to explore the sequence of occurrence and clonal origin of the two diseases....
BACKGROUND: This study aimed to improve the understanding of acute myeloid leukemia (AML) secondary to chronic lymphocytic leukemia (CLL), and to explore the sequence of occurrence and clonal origin of the two diseases. CASE REPORT: We reported a case of a 71-year-old man with a history of CLL. The patient was administrated with chlorambucil for 19 years and was admitted to our hospital due to fever. Then he was subjected with routine blood tests, bone marrow smear examination, flow cytometric immunophenotyping and cytogenetic analysis. A final diagnosis of AML-M2 secondary to CLL with -Y,del(4q),del(5q),-7,add(12p),der(17),der(18),-22,+mar was made. After rejecting the therapy with Azacitidine combined with B-cell lymphoma-2 (Bcl-2) inhibitor, the patient died of pulmonary infection. CONCLUSION: This case highlights the rare occurrence of AML secondary to CLL after prolonged chlorambucil therapy and the poor prognosis of such cases, underscoring the importance of enhanced assessment of these patients.
Expression and Correlation of MIF and ERK1/2 in Liver Cirrhosis and Hepatocellular Carcinoma Induced by Hepatitis B.
Jia D, Li B, Wang JK … +7 more , Wang P, Li CY, Lu LX, Tian WY, Yu XH, Zhang JC, Zheng Y
Pharmgenomics Pers Med · 2023 · PMID 37124953 · Full text
OBJECTIVE: To detect expression and phosphorylation level of macrophage migration inhibitor (MIF) and extracellular-regulated kinases 1 and 2 (ERK1/2) in hepatitis B-induced liver cirrhosis (HBILC) and hepatocellular car...
OBJECTIVE: To detect expression and phosphorylation level of macrophage migration inhibitor (MIF) and extracellular-regulated kinases 1 and 2 (ERK1/2) in hepatitis B-induced liver cirrhosis (HBILC) and hepatocellular carcinoma (HCC) with a background of HBILC and analyze the correlation of MIF and ERK1/2 with HBILC and HCC. METHODS: Twenty cases of normal liver tissues were collected as a control group, and 48 specimens of HBILC tissues and 48 specimens of HCC tissues were collected as the experimental group, which were assigned as the HBILC group and HCC group, respectively. All tissue specimens were processed into tissue chips. The expressions of MIF, ERK1/2, and their phosphorylated proteins were detected via immunohistochemistry, and MIF and ERK1/2 nucleic acid expressions were detected by in situ hybridization. The results were statistically analyzed using the chi-square test. RESULTS: Proteins and nucleic acids of MIF and ERK1/2 presented low expression in the control group and high expression in the HBILC group and HCC group. MIF expression in the three groups was 25.0%, 75.0%, and 79.17%, respectively, while that of the nucleic acids was 25.0%, 70.83%, and 68.75%, respectively. Expression of ERK1/2 in the three groups was 40.0%, 60.42%, and 81.25%, respectively, and that of nucleic acids was 40.0%, 79.17%, and 77.08%. Expression of pERK1/2 was low in the control and HBILC group and high in the HCC group. Expression of pERK1/2 in the three groups was 20%, 45.83%, and 75%, respectively. Expression of pERK1/2 in the HCC group was significantly different from that in the HBILC and control group (<0.05), but the difference between the HBILC group and control group was not statistically significant (>0.05). CONCLUSION: Occurrence and development of HBILC and HCC are not only related to the high expression of MIF but also closely related to the activation of the ERK1/2 signaling pathway.
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