Anna Bollinger, Céline K Stäuble, Chiara Jeiziner, Florine M Wiss, Kurt E Hersberger, Markus L Lampert, Henriette E Meyer Zu Schwabedissen, Samuel S Allemann
Purpose: 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.
Patients and methods: 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.
Results: 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.
Conclusion: 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.
目的:药物遗传学(PGx)是个性化医疗的一个新兴方面,具有提高药物治疗有效性和安全性的潜力。然而,PGx检测仍未常规纳入临床实践。我们进行了一项观察性病例系列研究,将来自涵盖30个基因的市售面板测试的PGx信息整合到药物评价中。该研究的目的是确定在研究人群中最常成为药物-基因相互作用(DGI)对象的药物。患者和方法:在门诊和住院环境中,我们招募了142名出现药物不良反应(ADR)和/或治疗失败(TF)的患者。从个别患者收集的匿名数据被协调并转移到结构化数据库。结果:大多数患者的主要诊断为精神或行为障碍(ICD-10: F, 61%)、肌肉骨骼系统和结缔组织疾病(ICD-10: M, 21%)和循环系统疾病(ICD-10: I, 11%)。处方药物数量中位数达到每人7种,导致大多数患者使用多种药物(处方药物≥5种,65%)。142例患者中共发现559例疑似DGI。基因检测后,141例患者中64种不同药物和21种不同基因引起的324例疑似DGI(58%)与至少一种遗传变异相关。6个月后,62%的研究人群记录了基于pgx的药物调整,从而在亚组中确定了差异。结论:本研究的数据分析为PGx背景下的进一步研究重点提供了有价值的见解。结果表明,我们样本中的大多数患者代表了临床实践中PGx面板检测的合适目标群体,特别是那些服用精神或行为障碍、循环系统疾病、免疫疾病、疼痛相关疾病的患者,以及服用多种药物的患者。
{"title":"Genotyping of Patients with Adverse Drug Reaction or Therapy Failure: Database Analysis of a Pharmacogenetics Case Series Study.","authors":"Anna Bollinger, Céline K Stäuble, Chiara Jeiziner, Florine M Wiss, Kurt E Hersberger, Markus L Lampert, Henriette E Meyer Zu Schwabedissen, 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":null,"pages":null},"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}
Fan Zhang, Hao Peng, Chuanyi Fu, Yidong Deng, Mao Zhang, Wenan Li, Jian Zhong, Qing Zhou, Li Huang, Shuli Xiao, Jiannong Zhao
Background: 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.
Objective: This study aimed to evaluate the impacts of three genetic polymorphisms (rs369149111 in HTRA1, rs1803628 in GAS6 and rs9808753 in IFNGR2) on stroke susceptibility among the Chinese Han population.
Methods: 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).
Results: As demonstrated by the overall analysis, rs9808753 in IFNGR2 (allele: OR = 1.25, 95% CI = 1.06-1.47, p = 0.007; homozygous: OR = 1.59, 95% CI = 1.14-2.23, p = 0.007; dominant: OR = 1.31, 95% CI = 1.02-1.67, p = 0.032; recessive: OR = 1.42, 95% CI = 1.05-1.91, p = 0.022; additive: OR = 1.26, 95% CI = 1.07-1.48, p = 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 (p < 0.05). And rs1803628 in GAS6 was significantly associated with an increased susceptibility to stroke in non-smokers (p < 0.05).
Conclusion: A risk-increasing effect of IFNGR2 rs980875 on stroke was detected in this study, which further broadens the understanding of the relationship between genetic polymorphisms and stroke susceptibility.
背景:卒中致残率高,30%的卒中病例病因不明。准确的诊断和治疗需要考虑一些罕见的遗传和非遗传因素。目的:本研究旨在评价3个遗传多态性(HTRA1基因rs369149111、GAS6基因rs1803628、IFNGR2基因rs9808753)对中国汉族人群脑卒中易感性的影响。方法:采用Agena MassARRAY平台对623例脑卒中患者和572例健康对照的3个单核苷酸多态性(snp)进行基因分型。通过logistic回归分析计算优势比(ORs)和95%置信区间(CIs),评估三个snp与卒中易感性的关系。此外,通过多因素降维(MDR)分析SNP-SNP相互作用。结果:综合分析显示,rs9808753在IFNGR2(等位基因:OR = 1.25, 95% CI = 1.06 ~ 1.47, p = 0.007;纯合子:OR = 1.59, 95% CI = 1.14-2.23, p = 0.007;显性:OR = 1.31, 95% CI = 1.02-1.67, p = 0.032;隐性:OR = 1.42, 95% CI = 1.05-1.91, p = 0.022;加性:OR = 1.26, 95% CI = 1.07-1.48, p = 0.007)与卒中易感性增加相关。此外,分层分析显示rs9808753与≤64岁亚组、男性和饮酒者卒中风险增加相关(p < 0.05)。GAS6中rs1803628与非吸烟者卒中易感性增加显著相关(p < 0.05)。结论:本研究检测到IFNGR2 rs980875对脑卒中具有增加风险的作用,进一步拓宽了对遗传多态性与脑卒中易感性关系的认识。
{"title":"Association Between <i>HTRA1, GAS6</i> and <i>IFNGR2</i> Gene Polymorphisms and Stroke Susceptibility in the Chinese Han Population.","authors":"Fan Zhang, Hao Peng, Chuanyi Fu, Yidong Deng, Mao Zhang, Wenan Li, Jian Zhong, Qing Zhou, Li Huang, Shuli Xiao, 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":null,"pages":null},"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}
Eda Eken, David S Estores, Emily J Cicali, Kristin K Wiisanen, Julie A Johnson
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 CYP2C19 genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of CYP2C19 prior to prescribing PPIs. There are strong data to support the influence of CYP2C19 genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on H. pylori 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.
{"title":"A Pharmacogenetics-Based Approach to Managing Gastroesophageal Reflux Disease: Current Perspectives and Future Steps.","authors":"Eda Eken, David S Estores, Emily J Cicali, Kristin K Wiisanen, 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":null,"pages":null},"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}
Jia Huang, Haiyan Wu, Guiqiang Zhao, Yan Ma, Yunping An, Li Sun, Fuye Li, Shengling Wang
Background: 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.
Methods: 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 TSHB, PAX8, TPO, NKX2-5, and TSHR in all participants. We compared genotype and allele frequencies between cases and controls utilizing the chi-squared test, logistic regression analysis, and haplotype analysis.
Results: 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).
Conclusion: rs3754363 has a statistically significant protective effect on people with cretinism, while rs2277923 may play a greater role in promoting the development of neurocretinism.
背景:克汀病是先天性甲状腺功能减退症的一种亚型,是一种由甲状腺激素分泌不足或受体缺乏引起的内分泌紊乱。遗传异常在甲状腺功能障碍的发展中起着重要作用。方法:从新疆维吾尔自治区招募克汀病患者183例和健康人群119例,随机选取TSHB、PAX8、TPO、NKX2-5和TSHR基因29个标签单核苷酸多态性(tsnp)。我们利用卡方检验、逻辑回归分析和单倍型分析比较了病例和对照组之间的基因型和等位基因频率。结果:卡方检验发现单个SNP与克汀病相关(隐性模型:rs3754363, OR = 0.46, 95% CI = 0.27-0.80, P = 0.00519;基因型模型:P = 0.01677)。我们将神经型、黏液性水肿型和混合型分层,并在比较黏液性水肿型和神经型时确定另一个SNP与更高的风险相关(rs2277923)。结论:rs3754363对克汀症患者有统计学意义上的保护作用,而rs2277923可能对神经克汀症的发展有更大的促进作用。
{"title":"A Case-Control Study of the Relationship Between Genetic Polymorphism and Cretinism in Xinjiang.","authors":"Jia Huang, Haiyan Wu, Guiqiang Zhao, Yan Ma, Yunping An, Li Sun, Fuye Li, 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":null,"pages":null},"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}
Qiong Tang, Dai Gong, Xiao-Min Ye, Jun-Ru Xu, Yi-Can Yang, Li-Juan Yan, Li Zou, Xiang-Lan Wen
Craniofacial dysmorphism, cardiac abnormalities, ectodermal abnormalities, psychomotor delay, intellectual disability, and short stature are all hallmarks of the extremely rare disorder known as cardiofaciocutaneous syndrome (CFCS). Although CFCS is considered rare, approximately 300 cases have been documented in the literature. In this report, we discuss a patient diagnosed with CFCS without the typical heart malformations but with craniofacial features, skin abnormalities, intellectual disability, and short stature. Genetic testing revealed the presence of three potentially harmful variants: one in the MAP2K1 gene and two in the ATP2B3 and CDC42BPB genes, the significance of which is currently not yet found. Our findings in this case report suggest that the clinical symptoms of CFCS may be atypical, thereby expanding our understanding of the symptom spectrum of the disease. Simultaneously, the link between the clinical symptoms of the patient and the two unknown pathogenic variants has not been established. This case report supplements existing clinical reference material by providing valuable insights into the specific scenario.
{"title":"A Case Report of Cardiofaciocutaneous Syndrome with <i>MAP2K1</i> Pathogenic Variant.","authors":"Qiong Tang, Dai Gong, Xiao-Min Ye, Jun-Ru Xu, Yi-Can Yang, Li-Juan Yan, Li Zou, Xiang-Lan Wen","doi":"10.2147/PGPM.S411964","DOIUrl":"https://doi.org/10.2147/PGPM.S411964","url":null,"abstract":"<p><p>Craniofacial dysmorphism, cardiac abnormalities, ectodermal abnormalities, psychomotor delay, intellectual disability, and short stature are all hallmarks of the extremely rare disorder known as cardiofaciocutaneous syndrome (CFCS). Although CFCS is considered rare, approximately 300 cases have been documented in the literature. In this report, we discuss a patient diagnosed with CFCS without the typical heart malformations but with craniofacial features, skin abnormalities, intellectual disability, and short stature. Genetic testing revealed the presence of three potentially harmful variants: one in the <i>MAP2K1</i> gene and two in the <i>ATP2B3</i> and <i>CDC42BPB</i> genes, the significance of which is currently not yet found. Our findings in this case report suggest that the clinical symptoms of CFCS may be atypical, thereby expanding our understanding of the symptom spectrum of the disease. Simultaneously, the link between the clinical symptoms of the patient and the two unknown pathogenic variants has not been established. This case report supplements existing clinical reference material by providing valuable insights into the specific scenario.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":null,"pages":null},"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/1e/68/pgpm-16-817.PMC10497045.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260568","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}
Purpose: 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.
Patients and methods: 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.
Results: 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.
Conclusion: 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.
{"title":"Hydroxychloroquine Ameliorates Hematuria in Children with X-Linked Alport Syndrome: Retrospective Case Series Study.","authors":"Lei Sun, Xin-Yu Kuang, Jing Zhang, 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":null,"pages":null},"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}
Pingyi Wang, Hongyan Lu, Hao Rong, Yuhe Wang, Li Wang, Xue He, Dongya Yuan, Yongjun He, Tianbo Jin
Background: 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 CYP39A1 methylation and HAPE.
Methods: Peripheral blood samples were enrolled from 106 participants (53 HAPE patients and 53 healthy subjects) to study the association of CYP39A1 methylation with HAPE. DNA methylation site in the promoter region of CYP39A1 was detected by Sequenom MassARRAY EpiTYPER platform.
Results: 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 (p< 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 (p< 0.05). CYP39A1_3_CpG_21 and CYP39A1_4_CpG_3 exhibited a lower methylation level in HAPE than that in the controls (p< 0.05). The association analysis given that CYP39A1_1_CpG_2.3.4 (OR 2.56, p= 0.035), CYP39A1_5_CpG_6.7 (OR 3.99, p= 0.003), CYP39A1_5_CpG_9.10 (OR 3.99, p= 0.003), CYP39A1_5_CpG_16.17.18 (OR 2.53, p= 0.033), and CYP39A1_5_CpG_20 (OR 3.05, p= 0.031) are associated with an increased risk of HAPE. Whereas CYP39A1_1_CpG_5 (OR 0.33, p= 0.016) and CYP39A1_3_CpG_21 (OR 0.18, p= 0.005) have a protective role in HAPE. Besides, age-stratification analysis showed that CYP39A1_1_CpG_5 (OR 0.16, p= 0.014) and CYP39A1_3_CpG_21 (OR 0.08, p= 0.023) had a protective impact on HAPE in people aged ≤32 years. CYP39A1_5_CpG_6.7 (OR 6.70, p= 0.008) and CYP39A1_5_CpG_9.10 (OR 6.70, p= 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, p< 0.001) was significantly better than other CpG sites.
Conclusion: The methylation level of CYP39A1 was associated with a risk of HAPE in the Chinese population, which provided new perspective for preventing and diagnosing of HAPE.
{"title":"The Association of Methylation Level in the <i>CYP39A1</i> Gene with High Altitude Pulmonary Edema in the Chinese Population.","authors":"Pingyi Wang, Hongyan Lu, Hao Rong, Yuhe Wang, Li Wang, Xue He, Dongya Yuan, Yongjun He, 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":null,"pages":null},"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}
Bi-Hua Luo, Jian-Qing Huang, Chun-Yu Huang, Pan Tian, Ai-Zhen Chen, Wei-Hao Wu, Xiao-Mei Ma, Yue-Xing Yuan, Lian Yu
Objective: The objective of this study was to screen lymphoma radiotherapy-resistant genes using CRISPR activation (CRISPRa).
Methods: 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.
Results: A total of 16 radiotherapy-resistant genes, namely, C20orf203, MTFR1, TAF1L, MYADM, NIPSNAP1, ZUP1, RASL11A, PSMB2, PSMA6, OR8H3, TMSB4Y, CD300LF, EEF1A1, ATP6AP1L, TRAF3IP2, and SNRNP35, 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 MTFR1, NIPSNAP1, ZUP1, PSMB2, PSMA6, EEF1A1, TMSB4Y and TAF1L (p < 0.05). No significant difference in the mRNA expression of AKT3 or TRAF3IP2 (p > 0.05) was found between the two groups (p > 0.05).
Conclusion: 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.
{"title":"Screening of Lymphoma Radiotherapy-Resistant Genes with CRISPR Activation Library.","authors":"Bi-Hua Luo, Jian-Qing Huang, Chun-Yu Huang, Pan Tian, Ai-Zhen Chen, Wei-Hao Wu, Xiao-Mei Ma, Yue-Xing Yuan, 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":null,"pages":null},"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}
Ziwen Mao, Weyland Cheng, Zhenwei Li, Manye Yao, Keming Sun
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.
{"title":"Clinical Associations of Bitter Taste Perception and Bitter Taste Receptor Variants and the Potential for Personalized Healthcare.","authors":"Ziwen Mao, Weyland Cheng, Zhenwei Li, Manye Yao, 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":null,"pages":null},"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}
Mir Sadat-Ali, Hussain K Al-Omar, Khalid W AlTabash, Ammar K AlOmran, Dakheel A AlDakheel, Hasan N AlSayed
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 ANXA3, BMP2, CALY, CYR61, FGFR1, IL1β, NOG, NOS2, PDGF gene, and TACR1 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.
{"title":"Genetic Influence of Fracture Nonunion (FNU): A Systematic Review.","authors":"Mir Sadat-Ali, Hussain K Al-Omar, Khalid W AlTabash, Ammar K AlOmran, Dakheel A AlDakheel, 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":null,"pages":null},"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}