Pharmacogenomics & Personalized Medicine最新文献

{"title":"Genetic Variants of <i>CYP4F2</i> Associated with Ischemic Stroke Susceptibility in the Han Population from Southern China.","authors":"Kang Huang,&nbsp;Tianyi Ma,&nbsp;Qiang Li,&nbsp;Yilei Zhou,&nbsp;Ting Qin,&nbsp;Zanrui Zhong,&nbsp;Shilin Tang,&nbsp;Wei Zhang,&nbsp;Jianghua Zhong,&nbsp;Shijuan Lu","doi":"10.2147/PGPM.S413632","DOIUrl":"https://doi.org/10.2147/PGPM.S413632","url":null,"abstract":"<p><strong>Background: </strong>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 <i>CYP4F2</i> gene polymorphism and susceptibility to IS.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Mutant allele \"A\" (OR = 1.24) and genotype \"AA\" (OR = 1.49) or \"GA\" (OR = 1.26) of <i>CYP4F2-</i>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/m², and smoking or drinking volunteers. <i>CYP4F2</i>-rs3093106 and -rs3093105 are associated with susceptibility to IS among smoking, drinking subjects, or IS patients complicated with hypertension.</p><p><strong>Conclusion: </strong><i>CYP4F2</i>-rs2108622, -rs3093106, and -rs3093105 are associated with an increased risk of IS.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"599-607"},"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/19/4a/pgpm-16-599.PMC10278860.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9712581","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":"Association Between <i>HTRA1, GAS6</i> and <i>IFNGR2</i> Gene Polymorphisms and Stroke Susceptibility in the Chinese Han Population.","authors":"Fan Zhang,&nbsp;Hao Peng,&nbsp;Chuanyi Fu,&nbsp;Yidong Deng,&nbsp;Mao Zhang,&nbsp;Wenan Li,&nbsp;Jian Zhong,&nbsp;Qing Zhou,&nbsp;Li Huang,&nbsp;Shuli Xiao,&nbsp;Jiannong Zhao","doi":"10.2147/PGPM.S408911","DOIUrl":"https://doi.org/10.2147/PGPM.S408911","url":null,"abstract":"<p><strong>Background: </strong>Stroke has a high disability rate, and 30% of stroke cases have an unknown cause. Accurate diagnosis and treatment of stroke requires consideration of several rare heritable and non-heritable factors.</p><p><strong>Objective: </strong>This study aimed to evaluate the impacts of three genetic polymorphisms (rs369149111 in <i>HTRA1</i>, rs1803628 in <i>GAS6</i> and rs9808753 in <i>IFNGR2</i>) on stroke susceptibility among the Chinese Han population.</p><p><strong>Methods: </strong>Three single nucleotide polymorphisms (SNPs) from 623 stroke cases and 572 healthy controls were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the associations of three SNPs with stroke susceptibility. Additionally, SNP-SNP interactions were analyzed by multifactor dimensionality reduction (MDR).</p><p><strong>Results: </strong>As demonstrated by the overall analysis, rs9808753 in <i>IFNGR2</i> (allele: OR = 1.25, 95% CI = 1.06-1.47, <i>p</i> = 0.007; homozygous: OR = 1.59, 95% CI = 1.14-2.23, <i>p</i> = 0.007; dominant: OR = 1.31, 95% CI = 1.02-1.67, <i>p</i> = 0.032; recessive: OR = 1.42, 95% CI = 1.05-1.91, <i>p</i> = 0.022; additive: OR = 1.26, 95% CI = 1.07-1.48, <i>p</i> = 0.007) was associated with an increased susceptibility to stroke. Besides, stratification analysis suggested that rs9808753 was associated with an increased risk of stroke in subgroup aged ≤ 64 years, males and drinkers (<i>p</i> < 0.05). And rs1803628 in <i>GAS6</i> was significantly associated with an increased susceptibility to stroke in non-smokers (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>A risk-increasing effect of <i>IFNGR2</i> rs980875 on stroke was detected in this study, which further broadens the understanding of the relationship between genetic polymorphisms and stroke susceptibility.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"717-727"},"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/58/b7/pgpm-16-717.PMC10335315.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9807182","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":"Genotyping of Patients with Adverse Drug Reaction or Therapy Failure: Database Analysis of a Pharmacogenetics Case Series Study.","authors":"Anna Bollinger,&nbsp;Céline K Stäuble,&nbsp;Chiara Jeiziner,&nbsp;Florine M Wiss,&nbsp;Kurt E Hersberger,&nbsp;Markus L Lampert,&nbsp;Henriette E Meyer Zu Schwabedissen,&nbsp;Samuel S Allemann","doi":"10.2147/PGPM.S415259","DOIUrl":"https://doi.org/10.2147/PGPM.S415259","url":null,"abstract":"<p><strong>Purpose: </strong>Pharmacogenetics (PGx) is an emerging aspect of personalized medicine with the potential to increase efficacy and safety of pharmacotherapy. However, PGx testing is still not routinely integrated into clinical practice. We conducted an observational case series study where PGx information from a commercially available panel test covering 30 genes was integrated into medication reviews. The aim of the study was to identify the drugs that are most frequently object of drug-gene-interactions (DGI) in the study population.</p><p><strong>Patients and methods: </strong>In out-patient and in-patient settings, we recruited 142 patients experiencing adverse drug reaction (ADR) and/or therapy failure (TF). Collected anonymized data from the individual patient was harmonized and transferred to a structured database.</p><p><strong>Results: </strong>The majority of the patients had a main diagnosis of a mental or behavioral disorder (ICD-10: F, 61%), of musculoskeletal system and connective tissue diseases (ICD-10: M, 21%), and of the circulatory system (ICD-10: I, 11%). The number of prescribed medicines reached a median of 7 per person, resulting in a majority of patients with polypharmacy (≥5 prescribed medicines, 65%). In total, 559 suspected DGI were identified in 142 patients. After genetic testing, an association with at least one genetic variation was confirmed for 324 suspected DGI (58%) caused by 64 different drugs and 21 different genes in 141 patients. After 6 months, PGx-based medication adjustments were recorded for 62% of the study population, whereby differences were identified in subgroups.</p><p><strong>Conclusion: </strong>The data analysis from this study provides valuable insights for the main focus of further research in the context of PGx. The results indicate that most of the selected patients in our sample represent suitable target groups for PGx panel testing in clinical practice, notably those taking drugs for mental or behavioral disorder, circulatory diseases, immunological diseases, pain-related diseases, and patients experiencing polypharmacy.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"693-706"},"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/5c/15/pgpm-16-693.PMC10327911.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9808387","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 Review of the Pharmacokinetic Characteristics of Immune Checkpoint Inhibitors and Their Clinical Impact Factors.","authors":"Jun-Chen Liu,&nbsp;Hong-Jing Yu","doi":"10.2147/PGPM.S391756","DOIUrl":"https://doi.org/10.2147/PGPM.S391756","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have been shown to be significant in improving the overall survival rate in certain malignancies with poor prognoses. However, only 20-40% of patients achieve long-term benefits, highlighting the relevance of the factors that influence the treatment, which can help clinicians improve their results and guide the development of new immune checkpoint therapies. In this study, the current pharmacokinetic aspects associated with the ICIs and the factors influencing clinical efficacy were characterised, including in terms of drug metabolism, drug clearance, hormonal effects and immunosuppressive effects.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"29-36"},"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/33/44/pgpm-16-29.PMC9880024.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10591018","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":"Rs11479 in <i>Thymidine Phosphorylase</i> Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.","authors":"Xiongjie Jia,&nbsp;Tao Zhang,&nbsp;Junjie Sun,&nbsp;Hengxue Lin,&nbsp;Tianliang Bai,&nbsp;Yating Qiao,&nbsp;Yaxin Li,&nbsp;Gang Li,&nbsp;Guicun Li,&nbsp;Xinyu Peng,&nbsp;Aimin Zhang","doi":"10.2147/PGPM.S397382","DOIUrl":"https://doi.org/10.2147/PGPM.S397382","url":null,"abstract":"<p><strong>Objective: </strong><i>Thymidine Phosphorylase (TYMP)</i> gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between <i>TYMP</i> polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy.</p><p><strong>Methods: </strong>A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of <i>TYMP</i> polymorphism and <i>TYMP</i> mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of <i>TYMP</i> according to genotype status was analyzed using non-parameter test.</p><p><strong>Results: </strong>Prevalence of rs11479 in <i>TYMP</i> among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (<i>P</i>=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (<i>P</i>=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (<i>P</i>=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, <i>P</i>=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of <i>TYMP</i> than that of patients with GG genotype (<i>P</i><0.001).</p><p><strong>Conclusion: </strong>Polymorphism rs11479 in <i>TYMP</i> gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of <i>TYMP</i>. The conclusion of this study should be validated in prospective clinical trials subsequently.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"277-289"},"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/4f/d2/pgpm-16-277.PMC10072144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9260035","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":"Acute Myeloid Leukemia Secondary to Chronic Lymphocytic Leukemia After Prolonged Chlorambucil Therapy: A Case Report.","authors":"Yan Wu,&nbsp;Shan Liu,&nbsp;Dongmei Wang,&nbsp;Xinjie Yao","doi":"10.2147/PGPM.S407940","DOIUrl":"https://doi.org/10.2147/PGPM.S407940","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Case report: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"401-405"},"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/61/7e/pgpm-16-401.PMC10150764.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9416257","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":"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}