Pharmacogenomics & Personalized Medicine最新文献

{"title":"Detection of Novel Pathogenic Variants in Two Families with Recurrent Fetal Congenital Heart Defects.","authors":"Rongqin Cai,&nbsp;Ya Tan,&nbsp;Mingming Wang,&nbsp;Huijun Yu,&nbsp;Jing Wang,&nbsp;Zhuo Ren,&nbsp;Zhe Dong,&nbsp;Yiwen He,&nbsp;Zhi Li,&nbsp;Li Lin,&nbsp;Ying Gu","doi":"10.2147/PGPM.S394120","DOIUrl":"https://doi.org/10.2147/PGPM.S394120","url":null,"abstract":"<p><strong>Background: </strong>Congenital heart disease (CHD) is the most common birth defect with strong genetic heterogeneity. To date, about 400 genes have been linked to CHD, including cell signaling molecules, transcription factors, and structural proteins that are important for heart development. Genetic analysis of CHD cases is crucial for clinical management and etiological analysis.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was performed to identify the genetic variants in two independent CHD cases with DNA samples from fetuses and their parents, followed by the exclusion of aneuploidy and large copy number variations (CNVs). The WES results were verified by Sanger sequencing.</p><p><strong>Results: </strong>In family A, a compound heterozygous variation in <i>PLD1</i> gene consisting of c.1132dupA (p.I378fs) and c.1171C>T (p.R391C) was identified in the fetus. The two variants were inherited from the father (c.1132dupA) and the mother (c.1171C>T), respectively. In family B, a hemizygous variant <i>ZIC3</i>: c.861delG (p.G289Afs*119) was identified in the fetus, which was inherited from the heterozygous mother. We further confirmed that these variants <i>PLD1</i>: c.1132dupA and <i>ZIC3</i>: c.861delG were novel.</p><p><strong>Conclusion: </strong>The findings in our study identified novel variants to the mutation spectrum of CHD and provided reliable evidence for the recurrent risk and reproductive care options to the affected families. Our study also demonstrates that WES has considerable prospects of clinical application in prenatal diagnosis.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"173-181"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/42/pgpm-16-173.PMC10008912.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9475734","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":"Serum Osteopontin, KL-6, and Syndecan-4 as Potential Biomarkers in the Diagnosis of Coal Workers' Pneumoconiosis: A Case-Control Study.","authors":"Zhifei Hou,&nbsp;Xinran Zhang,&nbsp;Yong Gao,&nbsp;Jing Geng,&nbsp;Yu Jiang,&nbsp;Huaping Dai,&nbsp;Chen Wang","doi":"10.2147/PGPM.S409644","DOIUrl":"https://doi.org/10.2147/PGPM.S409644","url":null,"abstract":"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 p<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.","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"537-549"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/5c/pgpm-16-537.PMC10241210.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9645600","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 Methylation Level in the <i>CYP39A1</i> Gene with High Altitude Pulmonary Edema in the Chinese Population.","authors":"Pingyi Wang,&nbsp;Hongyan Lu,&nbsp;Hao Rong,&nbsp;Yuhe Wang,&nbsp;Li Wang,&nbsp;Xue He,&nbsp;Dongya Yuan,&nbsp;Yongjun He,&nbsp;Tianbo Jin","doi":"10.2147/PGPM.S397862","DOIUrl":"https://doi.org/10.2147/PGPM.S397862","url":null,"abstract":"<p><strong>Background: </strong>High altitude pulmonary edema (HAPE) is still the most common fatal disease at high altitudes. DNA methylation proceeds with an important role in HAPE progression. This study was designed to investigate the association between <i>CYP39A1</i> methylation and HAPE.</p><p><strong>Methods: </strong>Peripheral blood samples were enrolled from 106 participants (53 HAPE patients and 53 healthy subjects) to study the association of <i>CYP39A1</i> methylation with HAPE. DNA methylation site in the promoter region of <i>CYP39A1</i> was detected by Sequenom MassARRAY EpiTYPER platform.</p><p><strong>Results: </strong>Probability analysis showed that the methylation probabilities of CYP39A1_1_CpG_5 and CYP39A1_3_CpG_21 are significant differences between the cases and controls (<i>p</i>< 0.05). The methylation level analysis indicated that CYP39A1_1_CpG_2.3.4, CYP39A1_5_CpG_6.7, and CYP39A1_5_CpG_9.10 were higher methylation in HAPE compared to the controls (<i>p</i>< 0.05). CYP39A1_3_CpG_21 and CYP39A1_4_CpG_3 exhibited a lower methylation level in HAPE than that in the controls (<i>p</i>< 0.05). The association analysis given that CYP39A1_1_CpG_2.3.4 (OR 2.56, <i>p</i>= 0.035), CYP39A1_5_CpG_6.7 (OR 3.99, <i>p</i>= 0.003), CYP39A1_5_CpG_9.10 (OR 3.99, <i>p</i>= 0.003), CYP39A1_5_CpG_16.17.18 (OR 2.53, <i>p</i>= 0.033), and CYP39A1_5_CpG_20 (OR 3.05, <i>p</i>= 0.031) are associated with an increased risk of HAPE. Whereas CYP39A1_1_CpG_5 (OR 0.33, <i>p</i>= 0.016) and CYP39A1_3_CpG_21 (OR 0.18, <i>p</i>= 0.005) have a protective role in HAPE. Besides, age-stratification analysis showed that CYP39A1_1_CpG_5 (OR 0.16, <i>p</i>= 0.014) and CYP39A1_3_CpG_21 (OR 0.08, <i>p</i>= 0.023) had a protective impact on HAPE in people aged ≤32 years. CYP39A1_5_CpG_6.7 (OR 6.70, <i>p</i>= 0.008) and CYP39A1_5_CpG_9.10 (OR 6.70, <i>p</i>= 0.008) were related to an increased susceptibility to HAPE aged >32 years. Moreover, the diagnostic value of CYP39A1_3_CpG_21 (AUC = 0.712, <i>p</i>< 0.001) was significantly better than other CpG sites.</p><p><strong>Conclusion: </strong>The methylation level of <i>CYP39A1</i> was associated with a risk of HAPE in the Chinese population, which provided new perspective for preventing and diagnosing of HAPE.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"617-628"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/16/33/pgpm-16-617.PMC10290841.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10095445","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":"A Pharmacogenetics-Based Approach to Managing Gastroesophageal Reflux Disease: Current Perspectives and Future Steps.","authors":"Eda Eken,&nbsp;David S Estores,&nbsp;Emily J Cicali,&nbsp;Kristin K Wiisanen,&nbsp;Julie A Johnson","doi":"10.2147/PGPM.S371994","DOIUrl":"https://doi.org/10.2147/PGPM.S371994","url":null,"abstract":"<p><p>Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of <i>CYP2C19</i> genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of <i>CYP2C19</i> prior to prescribing PPIs. There are strong data to support the influence of <i>CYP2C19</i> genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on <i>H. pylori</i> and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"645-664"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/10/pgpm-16-645.PMC10296543.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096414","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":"A Case-Control Study of the Relationship Between Genetic Polymorphism and Cretinism in Xinjiang.","authors":"Jia Huang,&nbsp;Haiyan Wu,&nbsp;Guiqiang Zhao,&nbsp;Yan Ma,&nbsp;Yunping An,&nbsp;Li Sun,&nbsp;Fuye Li,&nbsp;Shengling Wang","doi":"10.2147/PGPM.S418722","DOIUrl":"https://doi.org/10.2147/PGPM.S418722","url":null,"abstract":"<p><strong>Background: </strong>Cretinism is a subtype of congenital hypothyroidism, an endocrine disorder resulting from inadequate thyroid hormone production or receptor deficiency. Genetic abnormalities play a major role in the development of thyroid dysfunction.</p><p><strong>Methods: </strong>We recruited 183 participants with cretinism and 119 healthy participants from the Xinjiang Uyghur Autonomous Region and randomly selected 29 tag single nucleotide polymorphisms (tSNPs) in <i>TSHB, PAX8, TPO, NKX2-5</i>, and <i>TSHR</i> in all participants. We compared genotype and allele frequencies between cases and controls utilizing the chi-squared test, logistic regression analysis, and haplotype analysis.</p><p><strong>Results: </strong>Using the chi-squared test, a single SNP was found to be associated with cretinism (recessive model: rs3754363, OR = 0.46, 95% CI = 0.27-0.80, P = 0.00519; genotype model: P = 0.01677). We stratified neurological, myxedematous, and mixed type and determined that another SNP was associated with a higher risk when comparing myxedematous type to the neurological type (rs2277923).</p><p><strong>Conclusion: </strong>rs3754363 has a statistically significant protective effect on people with cretinism, while rs2277923 may play a greater role in promoting the development of neurocretinism.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"785-794"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/b0/pgpm-16-785.PMC10460608.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112235","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 Influence of Fracture Nonunion (FNU): A Systematic Review.","authors":"Mir Sadat-Ali,&nbsp;Hussain K Al-Omar,&nbsp;Khalid W AlTabash,&nbsp;Ammar K AlOmran,&nbsp;Dakheel A AlDakheel,&nbsp;Hasan N AlSayed","doi":"10.2147/PGPM.S407308","DOIUrl":"https://doi.org/10.2147/PGPM.S407308","url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>ANXA3, BMP2, CALY, CYR61, FGFR1, IL1β, NOG, NOS2, PDGF gene, and TACR1</i> are prone to develop a nonunion of fractures.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"569-575"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/03/pgpm-16-569.PMC10254683.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621257","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":"Screening of Lymphoma Radiotherapy-Resistant Genes with CRISPR Activation Library.","authors":"Bi-Hua Luo,&nbsp;Jian-Qing Huang,&nbsp;Chun-Yu Huang,&nbsp;Pan Tian,&nbsp;Ai-Zhen Chen,&nbsp;Wei-Hao Wu,&nbsp;Xiao-Mei Ma,&nbsp;Yue-Xing Yuan,&nbsp;Lian Yu","doi":"10.2147/PGPM.S386085","DOIUrl":"https://doi.org/10.2147/PGPM.S386085","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to screen lymphoma radiotherapy-resistant genes using CRISPR activation (CRISPRa).</p><p><strong>Methods: </strong>The Human CRISPRa library virus was packaged and then transfected into lymphoma cells to construct an activation library cell line, which was irradiated at the minimum lethal radiation dose to screen radiotherapy-resistant cells. Radiotherapy-resistant cell single-guide RNA (sgRNA) was first amplified by quantitative polymerase chain reaction (qPCR) in the coding region and then subject to next-generation sequencing (NGS) and bioinformatics analysis to screen radiotherapy-resistant genes. Certain radiotherapy-resistant genes were then selected to construct activated cell lines transfected with a single gene so as to further verify the relationship between gene expression and radiotherapy resistance.</p><p><strong>Results: </strong>A total of 16 radiotherapy-resistant genes, namely, <i>C20orf203, MTFR1, TAF1L, MYADM, NIPSNAP1, ZUP1, RASL11A, PSMB2, PSMA6, OR8H3, TMSB4Y, CD300LF, EEF1A1, ATP6AP1L, TRAF3IP2</i>, and <i>SNRNP35</i>, were screened based on the NGS results and bioinformatics analysis of the radiotherapy-resistant cells. Activated cell lines transfected with a single gene were constructed using 10 radiotherapy-resistant genes. The qPCR findings showed that, when compared with the control group, the experimental group had significantly up-regulated mRNA expression of <i>MTFR1, NIPSNAP1, ZUP1, PSMB2, PSMA6, EEF1A1</i>, <i>TMSB4Y</i> and <i>TAF1L</i> (p < 0.05). No significant difference in the mRNA expression of <i>AKT3</i> or <i>TRAF3IP2</i> (p > 0.05) was found between the two groups (p > 0.05).</p><p><strong>Conclusion: </strong>The 16 genes screened are potential lymphoma radiotherapy-resistant genes. It was initially determined that the high expression of 8 genes was associated with lymphoma radiotherapy resistance, and these genes could serve as the potential biomarkers for predicting lymphoma radiotherapy resistance or as new targets for therapy.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"67-80"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/ef/pgpm-16-67.PMC9897072.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9231261","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":"Clinical Associations of Bitter Taste Perception and Bitter Taste Receptor Variants and the Potential for Personalized Healthcare.","authors":"Ziwen Mao,&nbsp;Weyland Cheng,&nbsp;Zhenwei Li,&nbsp;Manye Yao,&nbsp;Keming Sun","doi":"10.2147/PGPM.S390201","DOIUrl":"https://doi.org/10.2147/PGPM.S390201","url":null,"abstract":"<p><p>Bitter taste receptors (T2Rs) consist of 25 functional receptors that can be found in various types of cells throughout the human body with responses ranging from detecting bitter taste to suppressing pathogen-induced inflammation upon activation. Numerous studies have observed clinical associations with genetic or phenotypic variants in bitter taste receptors, most notably that of the receptor isoform T2R38. With genetic variants playing a role in the response of the body to bacterial quorum-sensing molecules, bacterial metabolites, medicinal agonists and nutrients, we examine how T2R polymorphisms, expression levels and bitter taste perception can lead to varying clinical associations. From these genetic and phenotypic differences, healthcare management can potentially be individualized through appropriately administering drugs with bitter masking to increase compliance; optimizing nutritional strategies and diets; avoiding the use of T2R agonists if this pathway is already activated from bacterial infections; adjusting drug regimens based on differing prognoses; or adjusting drug regimens based on T2R expression levels in the target cell type and bodily region.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"121-132"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/f2/pgpm-16-121.PMC9936560.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9317019","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":"Hydroxychloroquine Ameliorates Hematuria in Children with X-Linked Alport Syndrome: Retrospective Case Series Study.","authors":"Lei Sun,&nbsp;Xin-Yu Kuang,&nbsp;Jing Zhang,&nbsp;Wen-Yan Huang","doi":"10.2147/PGPM.S394290","DOIUrl":"https://doi.org/10.2147/PGPM.S394290","url":null,"abstract":"<p><strong>Purpose: </strong>As a rare collagen type IV hereditary kidney disease, X-linked Alport syndrome (XLAS) is the most common form of Alport syndrome, the prevalence of which is estimated at 1:10,000 of the population, four times higher than the prevalence rate of autosomal recessive Alport syndrome. To describe a series of eight XLAS children with persistent hematuria and proteinuria and the clinical outcomes after hydroxychloroquine (HCQ) treatment to assess its efficacy as early intervention.</p><p><strong>Patients and methods: </strong>The study retrospectively analysed 8 patients with persistent hematuria and proteinuria at different onset ages who were diagnosed with XLAS and been treated with HCQ. The urinary erythrocyte count, urinary albuminn were measured. Descriptive statistics were used to estimate the patients' responses to HCQ treatment after one month, three months, and six months.</p><p><strong>Results: </strong>After the first month, the three months, and the six months of HCQ treatment, the urinary erythrocyte counts of four, seven, and eight children were significantly reduced; the decreasing proteinuria was found in two, four, and five children. Only one child with increasing proteinuria was found after 1-month HCQ treatment. This proteinuria was maintained after 3-month HCQ treatment but decreased to minor after 6-month HCQ treatment.</p><p><strong>Conclusion: </strong>We present the first potential efficacy of HCQ treatment in XLAS with hematuria and persistent proteinuria. It suggested that HCQ could be an effective treatment to ameliorate hematuria and proteinuria.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"145-151"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7a/7b/pgpm-16-145.PMC9976585.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9411592","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":"Pharmacogenomics in the Management of Pulmonary Arterial Hypertension: Current Perspectives.","authors":"James C Coons,&nbsp;Philip E Empey","doi":"10.2147/PGPM.S361222","DOIUrl":"https://doi.org/10.2147/PGPM.S361222","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a rare disease with heterogeneous causes that can lead to right ventricular (RV) failure and death if left untreated. There are currently 10 medications representative of five unique pharmacologic classes that are approved for treatment. These have led to significant improvements in overall clinical outcome. However, substantial variability in dosing requirements and treatment response is evident, leading to suboptimal outcome for many patients. Furthermore, dosing is empiric and iterative and can lead to delays in meeting treatment goals and burdensome adverse effects. Pharmacogenomic (PGx) associations have been reported with certain PAH medications, such as treprostinil and bosentan, and can explain some of the variability in response. Relevant genes associated with treprostinil include <i>CYP2C8, CYP2C9, CAMK2D</i>, and <i>PFAS. CYP2C8</i> and <i>CYP2C9</i> are the genes encoding the major metabolizing liver enzymes for treprostinil, and reduced function variants (*2, *3) with <i>CYP2C9</i> were associated with lower treatment persistence. Additionally, a higher <i>CYP2C9</i> activity score was associated with a significantly less risk of treatment discontinuation. Other genes of interest that have been explored with treprostinil include <i>CAMK2D</i>, which is associated with right ventricular dysfunction and significantly higher dose requirements. Similarly, <i>PFAS</i> is associated with lower concentrations of cyclic adenosine monophosphate and significantly higher dose requirements. Genes of interest with the endothelin receptor antagonist (ERA) class include <i>GNG2</i> and <i>CYP2C9</i>. A genetic variant in <i>GNG2</i> (rs11157866) was linked to a significantly increased rate of clinical improvement with ERAs. The *2 variant with <i>CYP2C9</i> (encoding for the major metabolizing enzyme for bosentan) was significantly associated with a higher risk for elevations in hepatic aminotransferases and liver injury. In summary, this article reviews the relevant pharmacogenes that have been associated to date with dosing and outcome among patients who received PAH medications.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"729-737"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/55/pgpm-16-729.PMC10349598.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816647","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}