Pub Date : 2021-08-23DOI: 10.2174/1875692118666210823115347
J. Guerra, V. Naidoo, R. Cacabelos
Age-related hearing loss (ARHL) or presbycusis shares common features with conditions related to senescence and neurodegeneration. In this review, we explore the linking of genes involved in such processes with presbycusis, that has been proven to share important relationships with genes involved in dementia (APOE and MTHFR), ototoxicity (the GST group), and pharmacogenetics (NAT2). In this regard, we propose the construction of pharmacogenetics for the presbycusis database that could help better control side effects in this particularly vulnerable population susceptible to neurodegenerative disorders. Moreover, preliminary epigenetics studies have recently identified links in human genes involved in ARHL, which could serve as biomarkers or as therapeutic targets.
{"title":"Genomics and Pharmacogenomics of Age-Related Hearing Loss","authors":"J. Guerra, V. Naidoo, R. Cacabelos","doi":"10.2174/1875692118666210823115347","DOIUrl":"https://doi.org/10.2174/1875692118666210823115347","url":null,"abstract":"\u0000\u0000Age-related hearing loss (ARHL) or presbycusis shares common features with conditions related to senescence and neurodegeneration. In this review, we explore the linking of genes involved in such processes with presbycusis, that has been proven to share important relationships with genes involved in dementia (APOE and MTHFR), ototoxicity (the GST group), and pharmacogenetics (NAT2). In this regard, we propose the construction of pharmacogenetics for the presbycusis database that could help better control side effects in this particularly vulnerable population susceptible to neurodegenerative disorders. Moreover, preliminary epigenetics studies have recently identified links in human genes involved in ARHL, which could serve as biomarkers or as therapeutic targets. \u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75476032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-08-10DOI: 10.2174/1875692118666210810092755
Belgin Susleyici, C. Ciftci, S. Yurdakul, M. Çevik, C. Akdeniz, I. P. Canbolat, G. Deliorman, A. Karaalp
Clopidogrel is one of the most frequently prescribed antiplatelet agents to reduce the risk of atherosclerotic symptoms. CYP2C19 enzyme is involved in clopidogrel metabolism, and several genetic variations of CYP2C19gene are able to affect the clinical response of clopidogrel. Despite the lack of a fully accepted guideline for CYP2C19 pharmacogenetic testing before clopidogrel treatment by relevant communities, we believe that determination of the variant frequencies is important to predict the efficiency and possible clopidogrel related risks before the initiation of treatment on the basis of populations. Our aim was to determine the distribution of gene polymorphisms affecting the enzyme activity in Turkish cardiac patients prescribed clopidogrel. 54 clopidogrel prescribed patients were included in the study. The presence of CYP2C19*2, *3, *4, *5, *6, *7, *8, *9, *10 and *17 polymorphisms were investigated using a microarray platform. No variant allele was detected for *4, *5, *6, *7, *8, *9 and *10 polymorphisms. The genotype frequencies were detected as 38.89% for *1/*1, 16.67% for *1/*2, 11.11% for *2/*17, 1.85% for *1/*3, 1.85% for *2/*3, 27.78% for *1/*17 and 1.85% for *17/*17. According to genotype analysis, 1.85% of the patients were recorded as poor and 29.63% intermediate; whereas 27.78% as rapid and 1.85% ultra-rapid metabolizers. Although our study population does not consist of a high number of patients, since the high frequency of intermediate, rapid and ultra-rapid metabolizer patients were detected in relatively high frequencies, CYP2C19 polymorphisms should be taken into account for efficiency and possible clopidogrel related risks in Turkish cardiac patients.
{"title":"Prevalence of CYP2C19 Polymorphisms in Clopidogrel Treated Turkish Patients: Preliminary Results, 2017","authors":"Belgin Susleyici, C. Ciftci, S. Yurdakul, M. Çevik, C. Akdeniz, I. P. Canbolat, G. Deliorman, A. Karaalp","doi":"10.2174/1875692118666210810092755","DOIUrl":"https://doi.org/10.2174/1875692118666210810092755","url":null,"abstract":"\u0000\u0000 Clopidogrel is one of the most frequently prescribed antiplatelet agents to reduce the risk of atherosclerotic symptoms. CYP2C19 enzyme is involved in clopidogrel metabolism, and several genetic variations of CYP2C19gene are able to affect the clinical response of clopidogrel. Despite the lack of a fully accepted guideline for CYP2C19 pharmacogenetic testing before clopidogrel treatment by relevant communities, we believe that determination of the variant frequencies is important to predict the efficiency and possible clopidogrel related risks before the initiation of treatment on the basis of populations. Our aim was to determine the distribution of gene polymorphisms affecting the enzyme activity in Turkish cardiac patients prescribed clopidogrel. \u0000\u0000\u0000\u0000\u000054 clopidogrel prescribed patients were included in the study. The presence of CYP2C19*2, *3, *4, *5, *6, *7, *8, *9, *10 and *17 polymorphisms were investigated using a microarray platform. \u0000\u0000\u0000\u0000\u0000No variant allele was detected for *4, *5, *6, *7, *8, *9 and *10 polymorphisms. The genotype frequencies were detected as 38.89% for *1/*1, 16.67% for *1/*2, 11.11% for *2/*17, 1.85% for *1/*3, 1.85% for *2/*3, 27.78% for *1/*17 and 1.85% for *17/*17. According to genotype analysis, 1.85% of the patients were recorded as poor and 29.63% intermediate; whereas 27.78% as rapid and 1.85% ultra-rapid metabolizers. \u0000\u0000\u0000\u0000\u0000Although our study population does not consist of a high number of patients, since the high frequency of intermediate, rapid and ultra-rapid metabolizer patients were detected in relatively high frequencies, CYP2C19 polymorphisms should be taken into account for efficiency and possible clopidogrel related risks in Turkish cardiac patients. \u0000\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75023898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-28DOI: 10.2174/1875692118666210628122443
HariOm Singh, Vijay Chauware, Kamini Jakhar
Toll-like receptors (TLRs) act as mediators of an innate immune response to infectious agents. The risk for chronic infection and the development of cancer can be potentially influenced by the genetic variations in the TLR genes. TLR3 and TLR7 genes have been associated with susceptibility to several infections and immune diseases. Human population is very diverse. There are significant variations in the TLR3 and TLR7 polymorphisms among ethnic groups. Variations within the population are associated with the disease outcome. Hence, we aimed to compare the occurrence of TLR3 (rs5743312 C/T, rs3775296 C/A, and rs3775291 C/T) and TLR7 (rs179009 and rs179008) polymorphisms among healthy individuals of various populations. Genotyping TLR3 (rs5743312 C/T, rs3775296 C/A, and rs3775291 C/T) and TLR7 (rs179009 and rs179008) polymorphisms were done in 158 healthy controls from Western India by utilization of PCR-RFLP. In our study population, the prevalence of TLR3 rs5743312 CC, CT, and TT genotypes were found to be 67.1%, 31.0%, and 1.9%, respectively, whereas genotype distribution of rs3775296 C/A polymorphism was 65.2%, 31.6%, and 3.2%, respectively, and rs3775291C/T was 59.5%, 32.3% and 8.2%, respectively. The occurrence of TLR7 rs179008AA, rs179008AT, rs179008TT genotypes and rs179008A, rs179008T alleles in the healthy individuals were found to be 81.0%, 16.5%, 2.5% and 89.24%, 10.75%, respectively. The prevalence of TLR7 rs179009AA, rs179009AG, rs179009GG genotypes and rs179009A, rs179009G alleles in healthy individuals were 63.3%, 29.1%, 7.6% and 63.3%, 36.7%, respectively. The frequency of TLR7 polymorphism was compared with Italian, Asian, European, African, German, and France populations. The frequency of TLR3 polymorphism was compared with Asians, Caucasians, Taiwanese, Caucasians and Saudi Arabians, Poland, Taiwanese, Italy, Taiwan, Estonia, Asia, and the Caucasus. The inter-population differences were observed in the distribution of TLR3 and TLR7 polymorphisms. The prevalence of TLR3 and TLR7 polymorphisms suggested that genotype-phenotype studies should be conducted among population to address the innate immune responses against pathogens.
{"title":"Comparative Occurrence of TLR3 and TLR7 Polymorphisms among Healthy Individual of Various Population","authors":"HariOm Singh, Vijay Chauware, Kamini Jakhar","doi":"10.2174/1875692118666210628122443","DOIUrl":"https://doi.org/10.2174/1875692118666210628122443","url":null,"abstract":"\u0000\u0000Toll-like receptors (TLRs) act as mediators of an innate immune response to infectious agents. The risk for chronic infection and the development of cancer can be potentially influenced by the genetic variations in the TLR genes. TLR3 and TLR7 genes have been associated with susceptibility to several infections and immune diseases. Human population is very diverse. There are significant variations in the TLR3 and TLR7 polymorphisms among ethnic groups. Variations within the population are associated with the disease outcome. Hence, we aimed to compare the occurrence of TLR3 (rs5743312 C/T, rs3775296 C/A, and rs3775291 C/T) and TLR7 (rs179009 and rs179008) polymorphisms among healthy individuals of various populations.\u0000\u0000\u0000\u0000\u0000 Genotyping TLR3 (rs5743312 C/T, rs3775296 C/A, and rs3775291 C/T) and TLR7 (rs179009 and rs179008) polymorphisms were done in 158 healthy controls from Western India by utilization of PCR-RFLP.\u0000\u0000\u0000\u0000\u0000 In our study population, the prevalence of TLR3 rs5743312 CC, CT, and TT genotypes were found to be 67.1%, 31.0%, and 1.9%, respectively, whereas genotype distribution of rs3775296 C/A polymorphism was 65.2%, 31.6%, and 3.2%, respectively, and rs3775291C/T was 59.5%, 32.3% and 8.2%, respectively. The occurrence of TLR7 rs179008AA, rs179008AT, rs179008TT genotypes and rs179008A, rs179008T alleles in the healthy individuals were found to be 81.0%, 16.5%, 2.5% and 89.24%, 10.75%, respectively. The prevalence of TLR7 rs179009AA, rs179009AG, rs179009GG genotypes and rs179009A, rs179009G alleles in healthy individuals were 63.3%, 29.1%, 7.6% and 63.3%, 36.7%, respectively. The frequency of TLR7 polymorphism was compared with Italian, Asian, European, African, German, and France populations. The frequency of TLR3 polymorphism was compared with Asians, Caucasians, Taiwanese, Caucasians and Saudi Arabians, Poland, Taiwanese, Italy, Taiwan, Estonia, Asia, and the Caucasus. The inter-population differences were observed in the distribution of TLR3 and TLR7 polymorphisms. \u0000\u0000\u0000\u0000\u0000The prevalence of TLR3 and TLR7 polymorphisms suggested that genotype-phenotype studies should be conducted among population to address the innate immune responses against pathogens. \u0000\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89901271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-16DOI: 10.2174/1875692118666210616165145
Nymphaea Arora, Vikash Prashar, Tania Arora, R. Sidhu, Anshul Mishra, P. Godara, Arpita Banerjee, Arti Sharma, J. Parkash
Nitric oxide (NO) is a diatomic free radical gaseous molecule that is formed from L-arginine through NOS (Nitric oxide synthase) catalyzed reaction. NO controls vascular tone (hence blood pressure), insulin secretion, airway tone, and peristalsis and is involved in angiogenesis (growth of new blood vessels) and in the development of the nervous system. In the CNS, NO is an important messenger molecule, which is involved in various major functions in the brain. NOS has been classified into three isoforms which include nNOS (neuronal NOS), eNOS (endothelial NOS), and iNOS (inducible NOS). NOS1 is localized on chromosome 12, consisting of 1434 amino acids and 161 KDa molecular weight. nNOS is involved in synaptic transmission, regulating the tone of smooth muscles, penile erection. We studied NOS1 gene and protein network analysis through in silico techniques as human nNOS sequence was fetched from GenBank, and its homologous sequences were retrieved through BLAST search. Moreover, the results of this study exploit the role of NOS1 in various pathways, which provide ways to regulate it in various neurodegenerative diseases. Previous research has revealed the role of Nitric Oxide (NO) formed from L-arginine through NOS (Nitric Oxide Synthase) as a physiological inter/intracellular messenger in the central as well as the peripheral nervous system. The diverse functions of NOS include insulin secretion, airway tone, vascular tone regulation, and in the brain, it is involved in differentiation, development, synaptic plasticity, and neurosecretion. The objective of this study is to unravel the role of neuronal Nitric Oxide Synthase (nNOS) in different pathways and its involvement as a therapeutic target in various neurodegenerative disorders, which can surely provide ways to regulate its activity in different aspects. In this study, we employed various bioinformatics tools and databases, initiating the study by fetching the neuronal Nitric Oxide Synthase (nNOS) sequence(GenBank) to find its homologous sequences(BLAST) and then exploring its physical properties and post-translational modifications, enhancing the research by network analysis(STRING), leading to its functional enrichment(Panther). The results positively support the hypothesis of its role in various pathways related to neurodegeneration., Its interacting partners are the probable therapeutic targets of various neurodegenerative diseases focusing on specifically multi-target analysis. This study considered the evolutionary trend of physical, chemical, and biological properties of NOS1 through different phyla. The neuronal Nitric Oxide Synthase (nNOS), being one of the three isoforms of NOS (Nitric Oxide Synthase), is found to be involved in more pathways than just forming Nitric Oxide. This research provides the base for further neurological research.
{"title":"Comparative Genomic and Network Analysis of nNOS by Using Different Bioinformatics Approaches","authors":"Nymphaea Arora, Vikash Prashar, Tania Arora, R. Sidhu, Anshul Mishra, P. Godara, Arpita Banerjee, Arti Sharma, J. Parkash","doi":"10.2174/1875692118666210616165145","DOIUrl":"https://doi.org/10.2174/1875692118666210616165145","url":null,"abstract":"\u0000\u0000 Nitric oxide (NO) is a diatomic free radical gaseous molecule that is formed from L-arginine through NOS (Nitric oxide synthase) catalyzed reaction. NO controls vascular tone (hence blood pressure), insulin secretion, airway tone, and peristalsis and is involved in angiogenesis (growth of new blood vessels) and in the development of the nervous system. In the CNS, NO is an important messenger molecule, which is involved in various major functions in the brain. NOS has been classified into three isoforms which include nNOS (neuronal NOS), eNOS (endothelial NOS), and iNOS (inducible NOS). NOS1 is localized on chromosome 12, consisting of 1434 amino acids and 161 KDa molecular weight. nNOS is involved in synaptic transmission, regulating the tone of smooth muscles, penile erection. We studied NOS1 gene and protein network analysis through in silico techniques as human nNOS sequence was fetched from GenBank, and its homologous sequences were retrieved through BLAST search. Moreover, the results of this study exploit the role of NOS1 in various pathways, which provide ways to regulate it in various neurodegenerative diseases. \u0000\u0000\u0000\u0000Previous research has revealed the role of Nitric Oxide (NO) formed from L-arginine through NOS (Nitric Oxide Synthase) as a physiological inter/intracellular messenger in the central as well as the peripheral nervous system. The diverse functions of NOS include insulin secretion, airway tone, vascular tone regulation, and in the brain, it is involved in differentiation, development, synaptic plasticity, and neurosecretion. \u0000\u0000\u0000\u0000The objective of this study is to unravel the role of neuronal Nitric Oxide Synthase (nNOS) in different pathways and its involvement as a therapeutic target in various neurodegenerative disorders, which can surely provide ways to regulate its activity in different aspects.\u0000\u0000\u0000\u0000 In this study, we employed various bioinformatics tools and databases, initiating the study by fetching the neuronal Nitric Oxide Synthase (nNOS) sequence(GenBank) to find its homologous sequences(BLAST) and then exploring its physical properties and post-translational modifications, enhancing the research by network analysis(STRING), leading to its functional enrichment(Panther).\u0000\u0000\u0000\u0000\u0000 The results positively support the hypothesis of its role in various pathways related to neurodegeneration., Its interacting partners are the probable therapeutic targets of various neurodegenerative diseases focusing on specifically multi-target analysis.\u0000\u0000\u0000\u0000This study considered the evolutionary trend of physical, chemical, and biological properties of NOS1 through different phyla. The neuronal Nitric Oxide Synthase (nNOS), being one of the three isoforms of NOS (Nitric Oxide Synthase), is found to be involved in more pathways than just forming Nitric Oxide. This research provides the base for further neurological research.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82130363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-03DOI: 10.2174/1875692118666210603155248
Maja Stoneberg, Natasha J. Petry, C. Grindeland, Monte Roemmich, Amanda Massmann, Jordan F Baye, April Schultz
The impact of personalized medicine is potentially enormous, but the genetic results are often difficult to integrate into health settings. A number of research studies are emerging to aid in translating pharmacogenomics into clinical practice. We aimed to create a standardized process to guide the implementation of dose adjustment recommendations into the electronic health record (EHR). Monographs were created for selected drug-gene pairs allowing for standardized review of available evidence. A scoring template was developed to assess whether the evidence presented in the drug monograph qualified said drug-gene pair for Clinical Decision Support (CDS) within the EHR. Of nine medications reviewed, only one drug-gene pair qualified for a CDS proposal to the institution’s governing pharmacogenomics committee. This project resulted in the development of a standard process for review to analyze pharmacogenomics literature allowing for CDS proposals.
{"title":"Developing a Standardized Review Process of Pharmacogenomics Resources for Psychotropic Medications","authors":"Maja Stoneberg, Natasha J. Petry, C. Grindeland, Monte Roemmich, Amanda Massmann, Jordan F Baye, April Schultz","doi":"10.2174/1875692118666210603155248","DOIUrl":"https://doi.org/10.2174/1875692118666210603155248","url":null,"abstract":"\u0000\u0000 The impact of personalized medicine is potentially enormous, but the genetic results are often difficult to integrate into health settings. A number of research studies are emerging to aid in translating pharmacogenomics into clinical practice.\u0000\u0000\u0000\u0000\u0000We aimed to create a standardized process to guide the implementation of dose adjustment recommendations into the electronic health record (EHR).\u0000\u0000\u0000\u0000\u0000Monographs were created for selected drug-gene pairs allowing for standardized review of available evidence. A scoring template was developed to assess whether the evidence presented in the drug monograph qualified said drug-gene pair for Clinical Decision Support (CDS) within the EHR.\u0000\u0000\u0000\u0000\u0000 Of nine medications reviewed, only one drug-gene pair qualified for a CDS proposal to the institution’s governing pharmacogenomics committee.\u0000\u0000\u0000\u0000\u0000 This project resulted in the development of a standard process for review to analyze pharmacogenomics literature allowing for CDS proposals.\u0000\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75405591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-25DOI: 10.2174/1875692118666210525150645
S. Granata, Alberto Verlato, V. Masola, A. Carraro, G. Santoro, F. Sallustio, G. Zaza
Solid organ transplantation is an available therapeutic option for cystic fibrosis (CF) patients without lung transplantation. However, the use of immunosuppressive agents may cause severe adverse events. In particular, patients treated with mTOR-inhibitors (mTOR-I) may aggravate pulmonary complications. It has been recently described that these drugs may induce epithelial to mesenchymal transition (EMT) of airway cells. The purpose of this study was to evaluate the effects of mTOR-I on primary bronchial epithelial cells carrying F508del. Human bronchial epithelial cells homozygous for F508del were treated with 5 and 100nM EVE for 24 hours and their RNA was extracted and hybridized to the Human HT-12 v3 Expression BeadChip (Illumina). Microarray results were validated by Real-Time PCR. Transepithelial resistance was measured by Millicell-ERS ohmmeter. High dosage EVE induced a significant up-regulation of 48 genes and a down-regulation of 14 genes. After pathway analysis by GSEA, we found that most of them were implicated in the inflammatory and pro-fibrotic pathways. Real-Time PCR confirmed that 100nM EVE was able to up-regulate some identified genes (IL-1 α IL-8, Pim-1) as well as pro-fibrotic elements ( α -SMA, connective tissue growth factor and metalloproteinase-12). Additionally, high dosage of EVE was also able to reduce the transepithelial resistance. In contrast, a lower level of EVE did not produce similar effects. Although performed in vitro, our study suggested that in solid organ transplant recipients with CF without a lung transplant, mTOR-I should be used at a low dosage to reduce its contribution to pulmonary inflammation and fibrosis.
{"title":"High-Dose Everolimus May Induce Pro-Inflammatory/Fibrotic Transcriptomic Changes In Bronchial Epithelial Cells From Cystic Fibrosis Patients.","authors":"S. Granata, Alberto Verlato, V. Masola, A. Carraro, G. Santoro, F. Sallustio, G. Zaza","doi":"10.2174/1875692118666210525150645","DOIUrl":"https://doi.org/10.2174/1875692118666210525150645","url":null,"abstract":"\u0000\u0000Solid organ transplantation is an available therapeutic option for cystic fibrosis (CF) patients without lung transplantation. However, the use of immunosuppressive agents may cause severe adverse events. In particular, patients treated with mTOR-inhibitors (mTOR-I) may aggravate pulmonary complications. It has been recently described that these drugs may induce epithelial to mesenchymal transition (EMT) of airway cells. \u0000\u0000\u0000\u0000The purpose of this study was to evaluate the effects of mTOR-I on primary bronchial epithelial cells carrying F508del.\u0000\u0000\u0000\u0000Human bronchial epithelial cells homozygous for F508del were treated with 5 and 100nM EVE for 24 hours and their RNA was extracted and hybridized to the Human HT-12 v3 Expression BeadChip (Illumina). Microarray results were validated by Real-Time PCR. Transepithelial resistance was measured by Millicell-ERS ohmmeter.\u0000\u0000\u0000\u0000High dosage EVE induced a significant up-regulation of 48 genes and a down-regulation of 14 genes. After pathway analysis by GSEA, we found that most of them were implicated in the inflammatory and pro-fibrotic pathways. Real-Time PCR confirmed that 100nM EVE was able to up-regulate some identified genes (IL-1 α IL-8, Pim-1) as well as pro-fibrotic elements ( α -SMA, connective tissue growth factor and metalloproteinase-12). Additionally, high dosage of EVE was also able to reduce the transepithelial resistance. In contrast, a lower level of EVE did not produce similar effects.\u0000\u0000\u0000\u0000Although performed in vitro, our study suggested that in solid organ transplant recipients with CF without a lung transplant, mTOR-I should be used at a low dosage to reduce its contribution to pulmonary inflammation and fibrosis.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86199505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-21DOI: 10.2174/1875692118666210421104202
HariOm Singh, S. Lata
Antiretroviral treatment (ART) have been reported to make changes in the functioning of dopaminergic neurons by altering the expression of dopamine active transporter (DAT). ART containing efavirenz drug have been related to show the adverse reactions on the central nervous system (CNS). Reported literature indicates the correlation of DAT19/10 genotype with the risk of progression of human immunodeficiency virus (HIV) infection. To assess the polymorphism in the human gene DAT1 including variable number tandem repeats (VNTR) from individuals having an infection of HIV. Genotyping was completed by performing a polymerase chain reaction (PCR) in a total of 165 HIV positive patients on ART treatment (34 were HIV-infected patients with hepatotoxicity, 131 HIV-infected patients) and 160 healthy controls without HIV infection. Incidence of DAT19/9, 8/9 genotypes, and allele with 9 repeats were higher in individuals having hepatotoxicity compared to those who do not have hepatotoxicity (5.9 vs. 0.8%, OR = 7.73; 2.9 vs. 0.8%, OR = 3.86; 20.58% vs. 14.12%, OR = 1.56). DAT19/10 genotype was related to severity of hepatotoxicity (OR = 1.86; P = 0.05). Upon comparison of genotype between individuals who do not have hepatotoxicity but having HIV infection and healthy controls without HIV infection, the dispersion of DAT1 10/11, 6/10 genotypes were greater in individuals with HIV infection (1.5% vs. 0.6%, OR = 2.73; 3.1% vs. 1.3%, OR = 2.73). DAT19/10 genotype was related to the people of advanced stage of HIV infection (OR = 2.05, P = 0.04). A higher incidence of DAT19/10 genotype was found in individuals with early stage of HIV infection than healthy controls (26.3 vs. 15.6%, OR = 1.93). In alcohol and tobacco consuming individuals with HIV infection and hepatotoxicity, DAT19/10 genotype has demonstrated hazard in the progression of HIV infection and increasing severity of hepatotoxic condition (OR = 1.40, P = 0.91, OR = 1.50; P = 0.91 and OR = 1.57, P = 0.39; OR = 2.70; P = 0.53). In patients with hepatotoxicity, nevirapine utilization with DAT19/10 genotype had demonstrated an increase in severity of hepatotoxicity (OR = 4.00, P = 0.41). In individuals with HIV infection and hepatotoxicity, alcohol and nevirapine usage along with DAT1 9/10 genotype have indicated a hazard for progression of HIV infection and increase in severity of hepatotoxicity (OR = 1.47, P = 0.85; OR = 1.73; P = 0.32). The genetic polymorphism with DAT19/10 genotype was linked with the progression of HIV infection and in the advancement of HIV-related illnesses.
据报道，抗逆转录病毒治疗(ART)通过改变多巴胺活性转运蛋白(DAT)的表达而改变多巴胺能神经元的功能。含有依非韦伦药物的抗逆转录病毒治疗已显示出对中枢神经系统的不良反应。文献报道表明，DAT19/10基因型与人类免疫缺陷病毒(HIV)感染进展的风险相关。评估人类基因DAT1的多态性，包括来自HIV感染个体的可变数串联重复序列(VNTR)。通过聚合酶链反应(PCR)对接受抗逆转录病毒治疗的165例HIV阳性患者(34例为肝毒性HIV感染患者，131例为HIV感染患者)和160例未感染HIV的健康对照进行基因分型。DAT19/9、8/9基因型和9重复等位基因在肝毒性个体中的发生率高于无肝毒性个体(5.9 vs. 0.8%， OR = 7.73;2.9 vs. 0.8%， OR = 3.86;20.58% vs. 14.12%， OR = 1.56)。DAT19/10基因型与肝毒性严重程度相关(OR = 1.86;P = 0.05)。通过比较无肝毒性但感染HIV的个体与未感染HIV的健康对照者的基因型，感染HIV的个体中DAT1 10/11、6/10基因型的分散度更大(1.5%比0.6%，OR = 2.73;3.1% vs. 1.3%， OR = 2.73)。DAT19/10基因型与HIV感染晚期相关(OR = 2.05, P = 0.04)。早期HIV感染者中DAT19/10基因型的发生率高于健康对照组(26.3% vs. 15.6%， OR = 1.93)。在有艾滋病毒感染和肝毒性的酒精和烟草消费个体中，DAT19/10基因型在艾滋病毒感染的进展和肝毒性状况的严重程度增加中显示出危险(OR = 1.40, P = 0.91, OR = 1.50;P = 0.91, OR = 1.57, P = 0.39;Or = 2.70;P = 0.53)。在肝毒性患者中，使用DAT19/10基因型的奈韦拉平会增加肝毒性的严重程度(OR = 4.00, P = 0.41)。在艾滋病毒感染和肝毒性的个体中，酒精和奈韦拉平的使用以及DAT1 /10基因型显示出艾滋病毒感染进展和肝毒性严重程度增加的危险(OR = 1.47, P = 0.85;Or = 1.73;P = 0.32)。具有DAT19/10基因型的遗传多态性与HIV感染的进展和HIV相关疾病的进展有关。
{"title":"Occurrence of DAT1 (VNTR) Polymorphism in Individuals with HIV infection","authors":"HariOm Singh, S. Lata","doi":"10.2174/1875692118666210421104202","DOIUrl":"https://doi.org/10.2174/1875692118666210421104202","url":null,"abstract":"\u0000\u0000Antiretroviral treatment (ART) have been reported to make changes in the functioning of dopaminergic neurons by altering the expression of dopamine active transporter (DAT). ART containing efavirenz drug have been related to show the adverse reactions on the central nervous system (CNS). Reported literature indicates the correlation of DAT19/10 genotype with the risk of progression of human immunodeficiency virus (HIV) infection. \u0000\u0000\u0000\u0000To assess the polymorphism in the human gene DAT1 including variable number tandem repeats (VNTR) from individuals having an infection of HIV. \u0000\u0000\u0000\u0000Genotyping was completed by performing a polymerase chain reaction (PCR) in a total of 165 HIV positive patients on ART treatment (34 were HIV-infected patients with hepatotoxicity, 131 HIV-infected patients) and 160 healthy controls without HIV infection. \u0000\u0000\u0000\u0000Incidence of DAT19/9, 8/9 genotypes, and allele with 9 repeats were higher in individuals having hepatotoxicity compared to those who do not have hepatotoxicity (5.9 vs. 0.8%, OR = 7.73; 2.9 vs. 0.8%, OR = 3.86; 20.58% vs. 14.12%, OR = 1.56). DAT19/10 genotype was related to severity of hepatotoxicity (OR = 1.86; P = 0.05). Upon comparison of genotype between individuals who do not have hepatotoxicity but having HIV infection and healthy controls without HIV infection, the dispersion of DAT1 10/11, 6/10 genotypes were greater in individuals with HIV infection (1.5% vs. 0.6%, OR = 2.73; 3.1% vs. 1.3%, OR = 2.73). DAT19/10 genotype was related to the people of advanced stage of HIV infection (OR = 2.05, P = 0.04). A higher incidence of DAT19/10 genotype was found in individuals with early stage of HIV infection than healthy controls (26.3 vs. 15.6%, OR = 1.93). In alcohol and tobacco consuming individuals with HIV infection and hepatotoxicity, DAT19/10 genotype has demonstrated hazard in the progression of HIV infection and increasing severity of hepatotoxic condition (OR = 1.40, P = 0.91, OR = 1.50; P = 0.91 and OR = 1.57, P = 0.39; OR = 2.70; P = 0.53). In patients with hepatotoxicity, nevirapine utilization with DAT19/10 genotype had demonstrated an increase in severity of hepatotoxicity (OR = 4.00, P = 0.41). In individuals with HIV infection and hepatotoxicity, alcohol and nevirapine usage along with DAT1 9/10 genotype have indicated a hazard for progression of HIV infection and increase in severity of hepatotoxicity (OR = 1.47, P = 0.85; OR = 1.73; P = 0.32). \u0000\u0000\u0000\u0000The genetic polymorphism with DAT19/10 genotype was linked with the progression of HIV infection and in the advancement of HIV-related illnesses. \u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81559137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-15DOI: 10.2174/1875692118666210315150037
M. Sai, Viswam Subeesh, S. HemaSreeGN, G. Saraswathy, N. Gouri
Nipah virus (NiV) is a zoonotic paramyxovirus that can cause severe respiratory illness and encephalitis in humans, with no effective targets and treatment. To investigate potential targets involved in the progression of NiV infection by bioinformatics studies. To identify the key gene involved in NiV infection, a microarray dataset (GSE32902) was downloaded from the National Centre of Biotechnology Information (NCBI). The differentially expressed genes were unraveled by using Geo2Enrichr and the functional enrichment analysis was identified by using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Search Tool for the Retrieval of Interacting Genes (STRING) was used to construct the Protein-protein interaction (PPI) network and visualized by using Cytoscape. A total of 500 genes (262 up-regulated and 238 down-regulated) were identified among NiV infected cells. 19 genes were found with a node degree of more than 10. All of them were upregulated genes. MX1, ISG15 and IFIT1 were found to have the highest node degree (degree = 20) followed by RSAD2 and IRF7 with node degree 18 and MX2 and IFIT3 with node degree 17. The above results explicitly demonstrate that the expressed genes attribute to a defensive response against the virus. Henceforth finding agonists for these genes would help in the effective management of Niv infection.
尼帕病毒是一种人畜共患副粘病毒，可引起人类严重呼吸道疾病和脑炎，没有有效的靶点和治疗方法。目的:通过生物信息学研究探讨NiV感染进展的潜在靶点。为了确定与NiV感染相关的关键基因，从国家生物技术信息中心(NCBI)下载了微阵列数据集(GSE32902)。差异表达基因通过geo2enrichment进行解析，功能富集分析通过Database for Annotation, Visualization, and Integrated Discovery (DAVID)进行鉴定。利用相互作用基因检索工具(STRING)构建蛋白-蛋白相互作用(PPI)网络，并利用Cytoscape进行可视化。在NiV感染细胞中共鉴定出500个基因，其中上调262个，下调238个。结度大于10的基因有19个。它们都是上调基因。节点度最高的是MX1、ISG15和IFIT1，节点度为20，其次是RSAD2和IRF7，节点度为18,MX2和IFIT3节点度为17。上述结果明确表明，表达的基因归因于对病毒的防御反应。因此，找到这些基因的激动剂将有助于有效地管理Niv感染。
{"title":"Prediction of Potential Targets of an Emerging Zoonotic Paramyxovirus: An Integrated Bioinformatics Analysis","authors":"M. Sai, Viswam Subeesh, S. HemaSreeGN, G. Saraswathy, N. Gouri","doi":"10.2174/1875692118666210315150037","DOIUrl":"https://doi.org/10.2174/1875692118666210315150037","url":null,"abstract":"\u0000\u0000 Nipah virus (NiV) is a zoonotic paramyxovirus that can cause severe respiratory illness and encephalitis in humans, with no effective targets and treatment.\u0000\u0000\u0000\u0000\u0000To investigate potential targets involved in the progression of NiV infection by bioinformatics studies.\u0000\u0000\u0000\u0000\u0000To identify the key gene involved in NiV infection, a microarray dataset (GSE32902) was downloaded from the National Centre of Biotechnology Information (NCBI). The differentially expressed genes were unraveled by using Geo2Enrichr and the functional enrichment analysis was identified by using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Search Tool for the Retrieval of Interacting Genes (STRING) was used to construct the Protein-protein interaction (PPI) network and visualized by using Cytoscape. \u0000\u0000\u0000\u0000\u0000A total of 500 genes (262 up-regulated and 238 down-regulated) were identified among NiV infected cells. 19 genes were found with a node degree of more than 10. All of them were upregulated genes. MX1, ISG15 and IFIT1 were found to have the highest node degree (degree = 20) followed by RSAD2 and IRF7 with node degree 18 and MX2 and IFIT3 with node degree 17. \u0000\u0000\u0000\u0000\u0000The above results explicitly demonstrate that the expressed genes attribute to a defensive response against the virus. Henceforth finding agonists for these genes would help in the effective management of Niv infection. \u0000\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73277318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-08DOI: 10.2174/1875692118666210308121530
Elif Gezer, M. Çevik, C. Akdeniz, I. P. Canbolat, S. Yurdakul, M. Sunbul, P. Çağatay, G. Deliorman, A. Karaalp, C. Ciftci, Belgin Susleyici
Coronary artery disease (CAD) is the one of the leading cause of morbidity and mortality worldwide and statins are frequently prescribed in the treatment of CAD to help lower blood cholesterol levels. Since the main enzyme involved in the metabolism of statins is CYP3A4, we aimed to investigate the effect of CYP3A4 * 1B genotypes on plasma lipid profile in Turkish cardiovascular disease subject with and without obesity taking statin. The study group consisted of 85 cardiovascular disease patients who were prescribed statins and had routine biochemical analysis data. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) assay were performed for genotyping of CYP3A4 *1B (rs2740574) polymorphism. Genotype distribution of CYP3A4 *1B polymorphism was found for homozygous wild (AA) and homozygous polymorphic (GG) genotypes as 94.1% and 5.9% respectively. We did not detect patients with heterozygous genotype in our study group. We found that the mean LDL-c, TG and TC levels were higher in patients with CYP3A4 *1B GG compared to AA genotype. The frequency of CYP3A4 *1B GG genotype frequency (9.5%) was detected higher in the obese patients compared to the non-obese patients (7.7%) (χ2=0.037, p=0.85). Our results demonstrate that CYP3A4 *1B homozygous polymorphic genotype distribution tend to be higher in obese patients compared to non- obese patients with cardiovascular disease which may point *1B allele to have a slight effect on serum lipids during statin therapy. Additional studies with higher samples are needed for evaluating the role of CYP3A4 *1B on lipids in patients under statin therapy.
{"title":"CYP3A4 *1B Gene Polymorphism in Coronary Artery Disease Patients with Obesity Undergoing Statin Treatment","authors":"Elif Gezer, M. Çevik, C. Akdeniz, I. P. Canbolat, S. Yurdakul, M. Sunbul, P. Çağatay, G. Deliorman, A. Karaalp, C. Ciftci, Belgin Susleyici","doi":"10.2174/1875692118666210308121530","DOIUrl":"https://doi.org/10.2174/1875692118666210308121530","url":null,"abstract":"\u0000\u0000Coronary artery disease (CAD) is the one of the leading cause of morbidity and mortality worldwide and statins are frequently prescribed in the treatment of CAD to help lower blood cholesterol levels. Since the main enzyme involved in the metabolism of statins is CYP3A4, we aimed to investigate the effect of CYP3A4 * 1B genotypes on plasma lipid profile in Turkish cardiovascular disease subject with and without obesity taking statin. \u0000\u0000\u0000\u0000\u0000The study group consisted of 85 cardiovascular disease patients who were prescribed statins and had routine biochemical analysis data. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) assay were performed for genotyping of CYP3A4 *1B (rs2740574) polymorphism. \u0000\u0000\u0000\u0000\u0000 Genotype distribution of CYP3A4 *1B polymorphism was found for homozygous wild (AA) and homozygous polymorphic (GG) genotypes as 94.1% and 5.9% respectively. We did not detect patients with heterozygous genotype in our study group. We found that the mean LDL-c, TG and TC levels were higher in patients with CYP3A4 *1B GG compared to AA genotype. The frequency of CYP3A4 *1B GG genotype frequency (9.5%) was detected higher in the obese patients compared to the non-obese patients (7.7%) (χ2=0.037, p=0.85). \u0000\u0000\u0000\u0000\u0000 Our results demonstrate that CYP3A4 *1B homozygous polymorphic genotype distribution tend to be higher in obese patients compared to non- obese patients with cardiovascular disease which may point *1B allele to have a slight effect on serum lipids during statin therapy. Additional studies with higher samples are needed for evaluating the role of CYP3A4 *1B on lipids in patients under statin therapy.\u0000\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89832790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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