Pharmacogenomics & Personalized Medicine最新文献

{"title":"The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.","authors":"Meghana Ram, Molly R Fraser, Junia Vieira Dos Santos, Rafail Tasakis, Ariana Islam, Jannah Usama Abo-Donia, Samir Parekh, Alessandro Lagana","doi":"10.2147/PGPM.S350238","DOIUrl":"https://doi.org/10.2147/PGPM.S350238","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. The disease's complexity is underpinned by a variety of genetic and molecular abnormalities that drive its progression.</p><p><strong>Methods: </strong>This review was conducted through a state-of-The-art literature search, primarily utilizing PubMed to gather peer-reviewed articles. We focused on the most comprehensive and cited studies to ensure a thorough understanding of the genetic and molecular landscapes of MM.</p><p><strong>Results: </strong>We detail primary and secondary alterations such as translocations, hyperdiploidy, single nucleotide variants (SNVs), copy number alterations (CNAs), gene fusions, epigenetic modifications, non-coding RNAs, germline predisposing variants, and the influence of the tumor microenvironment (TME). Our analysis highlights the heterogeneity of MM and the challenges it poses in treatment and prognosis, emphasizing the distinction between driver mutations, which actively contribute to oncogenesis, and passenger mutations, which arise due to genomic instability and do not contribute to disease progression.</p><p><strong>Conclusion & future perspectives: </strong>We report key controversies and challenges in defining the genetic drivers of MM, and examine their implications for future therapeutic strategies. We discuss the importance of systems biology approaches in understanding the dependencies and interactions among these alterations, particularly highlighting the impact of double and triple-hit scenarios on disease outcomes. By advancing our understanding of the molecular drivers and their interactions, this review sets the stage for novel therapeutic targets and strategies, ultimately aiming to improve clinical outcomes in MM patients.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"573-609"},"PeriodicalIF":1.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association of PLA2G7 Gene Polymorphisms with Serum Lp-PLA2 Activity and Lipid Profile in Han Chinese Patients with Coronary Heart Disease.","authors":"Yanhai Wang, Yupeng Shi, Zhongwei Wu, Jiangfeng Gao, Jing Wang, Lei Li, Yugang Wan, MuGu Lang A, Jianwen Zhang, Hongbo Wang, Yu Hou","doi":"10.2147/PGPM.S474494","DOIUrl":"https://doi.org/10.2147/PGPM.S474494","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and lipid profiles.</p><p><strong>Methods: </strong>A total of 93 han Chinese CHD patients were recruited. Serum Lp-PLA2 levels were determined using enzyme-linked immunosorbent assay (ELISA), while comprehensive analysis of PLA2G7 gene polymorphisms was conducted through whole-exome sequencing. Concurrently, multiple lipid parameters were measured and analyzed.</p><p><strong>Results: </strong>Among these Han Chinese CHD patients, the PLA2G7 gene rs1051931 (c.1136T>C p.Val379Ala) rare variant was highly prevalent (variant rate: 94.62%) among the study population, and showed negative correlation with serum Lp-PLA2 activity. The rs1765208290 (c.233G>A p.Gly78Asp) rare variant showed positive correlation with TG, ApoA, ApoB, HDL, LDL and TCHO levels in the serum. Strong linkage disequilibrium was observed between the rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe), both of which were related to lower Lp-PLA2 activity.</p><p><strong>Conclusion: </strong>In these Han Chinese CHD patients, the rs1051931 (c.1136T>C p.Val379Ala) rare variant in the PLA2G7 gene is closely linked to decreased Lp-PLA2 activity, whereas the rs1765208290 (c.233G>A p.Gly78Asp) rare variant influences lipid homeostasis. The strong LD between rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe) loci may act synergistically to reduce Lp-PLA2 activity.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"563-572"},"PeriodicalIF":1.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEAR1, PON1, CYP2C19, CYP1A2 and F2R Polymorphisms are Associated with MACE in Clopidogrel-Treated Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.","authors":"Pengqiang Du, Xingang Li, Dandan Li, Yongcheng Ma, Ming Ni, Yafei Li, Wenbo Li, Aifeng Wang, Xiaowei Xu","doi":"10.2147/PGPM.S490030","DOIUrl":"https://doi.org/10.2147/PGPM.S490030","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to evaluate the impact of clopidogrel-related gene polymorphisms on the occurrence of recurrent thrombotic events and cardiovascular death in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI).</p><p><strong>Methods: </strong>We conducted genotype testing for 26 specific loci mapped to 18 clopidogrel-associated genes in ACS patients who had undergone PCI and were receiving dual antiplatelet therapy only involving clopidogrel. We documented major adverse cardiovascular events (MACE) and clinical endpoints, analyzing the effect of genetic polymorphisms on treatment outcomes.</p><p><strong>Results: </strong>A total of 200 patients were enrolled in the study, with ischemic events occurring in 21 cases. Carriers of the T-allele for rs41273215 (<i>PEAR1</i>), rs662 (<i>PON1</i>), and the A-allele for rs4244285 (<i>CYP2C19</i>), as well as the C-allele for rs762551 (<i>CYP1A2</i>), exhibited a significant increase in the risk of MACE (OR = 2.76, 95% CI = 1.46-5.22, P = 0.002; OR = 3.72, 95% CI = 1.82-7.64, P = 0.0003; OR = 3.86, 95% CI = 1.89-7.86, P = 0.0002; OR = 2.40, 95% CI = 1.27-4.55, P = 0.007). Notably, the variant T-allele of rs168753 (<i>F2R</i>) was associated with a significant reduction in the risk of such events (OR = 0.29, 95% CI = 0.12-0.67, P = 0.004). No significant associations were found between other single nucleotide polymorphisms (SNPs) and clinical endpoints.</p><p><strong>Conclusion: </strong>Polymorphisms in rs41273215 (<i>PEAR1</i>), rs662 (<i>PON1</i>), rs4244285 (<i>CYP2C19</i>), and rs762551 (<i>CYP1A2</i>) were correlated with an increased risk of MACE in PCI patients. Conversely, the rs168753 (<i>F2R</i>) polymorphism was linked to improved cardiovascular outcomes. Genotyping for these polymorphisms could be instrumental in identifying patients at heightened risk for MACE.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"611-621"},"PeriodicalIF":1.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between the Polymorphisms in the Coding Sequence of SLCO1B1 and Blood Lipid Levels Before and After Treatment by Atorvastatin in the Chinese Han Adults with Dyslipidemia.","authors":"Chao Chen, Yan Tian, Fengshun Jia, Mingkun Feng, Guoqiang Zhang, Qian Li, Yanwei Zhang, Ningling Sun, Songnian Hu, Zheng Ji","doi":"10.2147/PGPM.S482289","DOIUrl":"https://doi.org/10.2147/PGPM.S482289","url":null,"abstract":"<p><strong>Purpose: </strong>Atorvastatin is commonly used to treat dyslipidemia; however, individual responses vary considerably. This study endeavors to evaluate the relationship between polymorphisms in the coding sequence (CDS) of SLCO1B1 gene and blood lipid levels before and after atorvastatin treatment among the Chinese Han adults with dyslipidemia.</p><p><strong>Patients and methods: </strong>A total of 165 Chinese Han adults undergoing atorvastatin therapy were enrolled in this study and followed up quarterly. The complete CDS of the SLCO1B1 gene was sequenced to detect polymorphisms. Statistical analysis was utilized to assess the impacts of sex, age, body mass index (BMI), and polymorphisms on blood lipid levels before and after atorvastatin treatment.</p><p><strong>Results: </strong>Fourteen polymorphisms were identified in the SLCO1B1 CDS. Among them, four polymorphisms had mutant alleles present in over 20 patients. No polymorphism was found to correlate with blood lipid levels before treatment; in contrast, age, sex, and BMI did show correlations (<i>P</i><0.05). Notably, females had higher baseline blood lipid levels than males, indicating that sex had a more significant impact on baseline levels than age and BMI. The polymorphism rs2306283 was significantly correlated with the efficacy of atorvastatin (<i>P</i><0.05), whereas age, sex, and BMI were not. Carriers of the rs2306283 AA allele experienced a substantially greater reduction in total cholesterol (TC) and triglyceride (TG) levels after atorvastatin treatment. The other polymorphisms did not demonstrate any significant impact on atorvastatin's efficacy.</p><p><strong>Conclusion: </strong>This study delved into the intricate genetic structure of polymorphisms in SLCO1B1 CDS and their roles in lipid metabolism and atorvastatin's efficacy among Chinese Han adults with dyslipidemia. The findings underscore the crucial role of the rs2306283 polymorphism in the response to atorvastatin's efficacy, highlighting the significance of pharmacogenomics in personalized medicine. It is thus advisable to consider genetic testing for SLCO1B1 variants to optimize atorvastatin therapy.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"551-561"},"PeriodicalIF":1.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD27 as a Diagnostic Biomarker and Its Role in Immune Heterogeneity and Predicting Clinical Drug Responses in Hashimoto's Thyroiditis.","authors":"Yan-Ming Dong, Guo-Qiang Bao","doi":"10.2147/PGPM.S487091","DOIUrl":"https://doi.org/10.2147/PGPM.S487091","url":null,"abstract":"<p><strong>Objective: </strong>To identify key genes and potential molecular mechanisms associated with Hashimoto's thyroiditis (HT) to provide new insights for the development of diagnostic and therapeutic targets for this disease.</p><p><strong>Methods: </strong>Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify the differentially expressed genes (DEGs) associated with HT. A protein-protein interaction (PPI) network was used to obtain hub genes, with CD27 emerging as the key gene in HT. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Set Enrichment Analysis (GSEA), and HT-infiltrating immune cell components as well as functions were performed to further investigate the role and potential mechanism of CD27 in cohorts with high and low expression of CD27.</p><p><strong>Results: </strong>CD27 was found to be upregulated in HT tissues and showed considerable clinical utility in HT. The CD27 of the high-expression cohort exhibited a higher enrichment in immune-related biological processes than the low-expression group. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis revealed that several activated HT-infiltrating immune cells were strongly associated with CD27, suggesting that CD27 has the potential to be a marker for the immune state in HT.</p><p><strong>Conclusion: </strong>In our study, CD27 was found to contribute to predicting clinical outcomes in patients with HT, including disease status and response to immunotherapy. CD27 is a promising biomarker for HT microenvironment remodeling, offering insights into new therapeutic approaches to improve treatment of HT.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"535-550"},"PeriodicalIF":1.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value and Immunological Role of POP7 in Clear Cell Renal Cell Carcinoma.","authors":"Ning Lou, Xiangui Meng, Tiexi Yu, Weiquan Li, Xin Lv, Weiwei Han, Wen Xiao, Ying Shi","doi":"10.2147/PGPM.S469247","DOIUrl":"https://doi.org/10.2147/PGPM.S469247","url":null,"abstract":"<p><strong>Background: </strong>Studies have found that RNA-binding proteins (RBPs) are participated in the occurrence or development of tumours. However, the role of processing of precursor family (POP family) in clear cell renal cell carcinoma (ccRCC) has not been studied yet. Here, we analyzed the expression and prognostic value of POP family in ccRCC analyzed and subsequently revealed the relationship between POP7 and immune infiltration in ccRCC patients.</p><p><strong>Methods: </strong>POP family expression in cancer and normal tissues was analyzed in Cancer Genome Atlas pan-cancer (TCGA-pan-cancer). Kaplan-Meier (KM) survival analysis, univariable and multivariable analysis demonstrated the survival of ccRCC with POP family in Kidney Clear Cell Carcinoma (TCGA-KIRC). POP7 mRNA and protein expression were verified by Gene Expression Omnibus (GEO) data, the quantitative real-time polymerase chain reaction (qRT-PCR), and Office of Cancer Clinical Proteomics Research (CPTAC). The diagnostic ability of POP7 mRNA and protein expression was achieved with ROC curves. Gene Set Enrichment Analysis (GSEA) and TiMER2 evaluated pathogenesis role and immune infiltration of POP7in ccRCC.</p><p><strong>Results: </strong>There is a significant difference in expression of POP family in TCGA-pan-cancer, especially in ccRCC. KM survival analysis, univariable and multivariable analysis demonstrated low expression of POP7 and was associated with poor OS and poor DFS. GEO data, the qRT-PCR, and CPTAC verified the high expression of POP7 mRNA and protein in ccRCC. ROC curves verified a valuable diagnostic ability of POP7 in mRNA and protein expression. GSEA demonstrated POP7 was associated with CD8+cells, CD4+cells, natural killer (NK) cells, and helper T (TH1) cells. TiMER2 results indicated POP7 had a positive correlation with T cell regulatory (Tregs) and myeloid-derived suppressor cells (MDSC) in ccRCC and was an immunosuppressor for ccRCC.</p><p><strong>Conclusion: </strong>POP7 was a reliable immunosuppressor, predictor and biomarker for ccRCC.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"521-534"},"PeriodicalIF":1.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0078767 Enhances Osteosarcoma Chemoresistance to Doxorubicin Through the Regulation of the miR-188-3p/GPX4 Axis.","authors":"Yin Tang, Yuzhe He, Lidong Wu","doi":"10.2147/PGPM.S473702","DOIUrl":"10.2147/PGPM.S473702","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is a primary malignancy of bone. The emergence of chemoresistance represents a persistent barrier to effective cancer patient care. This analysis sought to examine hsa_circ_0078767 as a mediator of doxorubicin (DOX) resistance in OS.</p><p><strong>Methods: </strong>Levels of hsa_circ_0078767, miR-188-3p, and glutathione peroxidase 4 (GPX4) in OS clinical tissue samples and cell lines were evaluated by quantitative polymerase chain reaction (qPCR) and Western blotting. Associations between hsa_circ_0078767 levels in clinical samples and patient overall survival were assessed with Kaplan-Meier curves. CCK-8 assays were utilized as a means of examining DOX half-inhibitory concentration (IC₅₀) values. RNA immunoprecipitation and pull-down, as well as reporter assays, investigated interactions between hsa_circ_0078767, miR-188-3p, and GPX4 within OS cells exhibiting DOX resistance.</p><p><strong>Results: </strong>OS patient tissues and cell lines resistant to DOX exhibited elevated hsa_circ_0078767 and GPX4 expression together with a reduction in miR-188-3p levels. Inhibiting hsa_circ_0078767 expression contributed to a profound decrease in the ability of OS tumors to resist DOX. Mechanistically, it was determined that hsa_circ_0078767 can enhance DOX chemoresistance through its ability to bind and sequester miR-188-3p, which otherwise negatively modulates GPX4 to enhance chemosensitivity. Accordingly, the sequestration of miR-188-3p by hsa_circ_0078767 led to the derepression and upregulation of GPX4.</p><p><strong>Conclusion: </strong>Hsa_circ_0078767 was found to modulate miR-188-3p/GPX4 signaling to enhance OS cell resistance to DOX treatment and facilitate disease progression. As such, hsa_circ_0078767 may represent a valuable biomarker or target for use in the context of OS patient management.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"511-520"},"PeriodicalIF":1.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Microenvironment Alterations and Identification of Key Diagnostic Biomarkers in Chronic Kidney Disease Using Integrated Bioinformatics and Machine Learning.","authors":"Jinbao Shi, Aliang Xu, Liuying Huang, Shaojie Liu, Binxuan Wu, Zuhong Zhang","doi":"10.2147/PGPM.S488143","DOIUrl":"10.2147/PGPM.S488143","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) involves complex immune dysregulation and altered gene expression profiles. This study investigates immune cell infiltration, differential gene expression, and pathway enrichment in CKD patients to identify key diagnostic biomarkers through machine learning methods.</p><p><strong>Methods: </strong>We assessed immune cell infiltration and immune microenvironment scores using the xCell algorithm. Differentially expressed genes (DEGs) were identified using the limma package. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed to evaluate pathway enrichment. Machine learning techniques (LASSO and Random Forest) pinpointed diagnostic genes. A nomogram model was constructed and validated for diagnostic prediction. Spearman correlation explored associations between key genes and immune cell recruitment.</p><p><strong>Results: </strong>The CKD group exhibited significantly altered immune cell infiltration and increased immune microenvironment scores compared to the normal group. We identified 2335 DEGs, including 124 differentially expressed immune-related genes. GSEA highlighted significant enrichment of inflammatory and immune pathways in the high immune score (HIS) subgroup, while GSVA indicated upregulation of immune responses and metabolic processes in HIS. Machine learning identified four key diagnostic genes: RGS1, IL4I1, NR4A3, and SOCS3. Validation in an independent dataset (GSE96804) and clinical samples confirmed their diagnostic potential. The nomogram model integrating these genes demonstrated high predictive accuracy. Spearman correlation revealed positive associations between the key genes and various immune cells, indicating their roles in immune modulation and CKD pathogenesis.</p><p><strong>Conclusion: </strong>This study provides a comprehensive analysis of immune alterations and gene expression profiles in CKD. The identified diagnostic genes and the constructed nomogram model offer potent tools for CKD diagnosis. The immunomodulatory roles of RGS1, IL4I1, NR4A3, and SOCS3 warrant further investigation as potential therapeutic targets in CKD.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"497-510"},"PeriodicalIF":1.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Diversity Landscape in African Population: A Review of Implications for Personalized and Precision Medicine.","authors":"Olivier Sibomana","doi":"10.2147/PGPM.S485452","DOIUrl":"10.2147/PGPM.S485452","url":null,"abstract":"<p><strong>Introduction: </strong>Africa, a continent considered to be the cradle of human beings has the largest genetic diversity among its population than other continents. This review discusses the implications of this high African genetic diversity to the development of personalized and precision medicine.</p><p><strong>Methodology: </strong>A comprehensive search across PubMed, Google Scholar, Science Direct, DOAJ, AJOL, and the Cochrane Library electronic databases and manual Google searches was conducted using key terms \"genetics\", \"genetic diversity\", \"Africa\", \"precision medicine\", and \"personalized medicine\". Updated original and review studies focusing on the implications of African high genetic diversity on personalized and precision medicine were included. Included studies were thematically synthesized to elucidate their positive or negative implications for personalized healthcare, aiming to foster informed clinical practice and scientific inquiry.</p><p><strong>Results: </strong>African populations' high genetic diversity presents opportunities for personalized and precision medicine including improving pharmacogenomics, understanding gene interactions, discovering new variants, mapping disease genes, creating updated genomic reference panels, and validating biomarkers. However, challenges include underrepresentation in studies, scarcity of reference genomes, inaccuracy of genetic testing and interpretation, and ancestry misclassification. Addressing these requires the establishment of genomic research centers, increasing funding, creating biobanks and repositories, education, infrastructure, and international cooperation to enhance healthcare equity and outcomes through personalized and precision medicine.</p><p><strong>Conclusion: </strong>High African genetic diversity presents both positive and negative implications for personalized and precision medicine. Deep further research is recommended to harness the challenges and use the opportunities to develop customized treatments.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"487-496"},"PeriodicalIF":1.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenomic Study of Selected Genes Affecting Amlodipine Blood Pressure Response in Patients with Hypertension.","authors":"Asif Jan, Abdullah R Alanzi, Ramzi A Mothana, Jun-Ya Kaimori, Syed Shaukat Ali, Tahir Muhammad, Muhammad Saeed, Rani Akbar, Mehtab Khan","doi":"10.2147/PGPM.S481068","DOIUrl":"10.2147/PGPM.S481068","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the availability of various antihypertensive medications, the response to these medications varies among individuals. Understanding how individual genetic variations affect drugs treatment outcomes is a key area of focus in precision medicine. This study investigated the correlation between single nucleotide polymorphisms (SNPs) in selected genes (CACNA1C, CACNA1D, ABCB1, ACE, ADBR2, and NOS1AP) and the blood pressure (BP) control by amlodipine.</p><p><strong>Methods: </strong>Four hundred individuals of Pashtun ethnicity undergoing amlodipine treatment for hypertension were included in the present study and divided into the controlled (BP less than 140/90 mmHg) and uncontrolled (BP greater than 140/90 mmHg) hypertension groups. Blood samples (3 mL) were collected from each participant, and DNA was extracted using the Kit method. Ten SNPs in amlodipine pharmacogenes were selected and genotyped using real-time PCR with the TaqMan^® system. Logistic regression model was used to determine the association between SNPs and the amlodipine BP response.</p><p><strong>Results: </strong>Notable association were observed between SNP rs2239050/CACNA1C and amlodipine blood pressure response, with GG genotype carriers demonstrating a better response (P=0.004) than individuals carrying CC or CG genotypes. SNP rs312481/CACNA1D also exhibited a positive pharmacogenetic association, Individuals with the GG genotype showing a considerable reduction in BP (P=0.021) compared to participants with AA or GA genotypes. In case of SNP rs429/ACE individuals carrying TA genotype were less likely to achieve BP control (P=0.002) than AA genotype carriers.</p><p><strong>Conclusion: </strong>Our finding suggests that the SNPs rs2239050/CACNA1C, rs312481/CACNA1D and rs429/ACE influence amlodipine blood pressure response in patients with hypertension. It is recommended that prior knowledge of amlodipine associated pharmacogenetic variants is important that could improve its treatment outcomes in hypertensive patients.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"17 ","pages":"473-486"},"PeriodicalIF":1.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}