Ros Moxham, Andrew Tjokrowidjaja, Sophie Devery, Renée Smyth, Alison McLean, Darren M Roberts, Kathy H C Wu
BACKGROUND Pharmacogenomics (PG) testing is under-utilised in Australia. Our research provides Australia-specific data on the perspectives of patients who have had PG testing and those of the clinicians involved in their care, with the aim to inform wider adoption of PG into routine clinical practice. AIM To investigate the frequency of actionable drug gene interactions and assess the perceived utility of PG among patients and clinicians METHODS We conducted a retrospective audit of PG undertaken by 100 patients at an Australian public hospital genetics service from 2018 to 2021. Via electronic surveys we compared and contrasted the experience, understanding and usage of results between these patients and their clinicians. RESULTS Of 100 patients who had PG, 84% were taking prescription medications, of which 67% were taking medications with actionable drug-gene interactions. Twenty-five out of 81 invited patients and 17 out of 89 invited clinicians completed the surveys. Sixty-eight percent of patients understood their PG results and 48% had medications changed following testing. Paired patient-clinician surveys showed patient-perceived utility and experience was positive, contrasting their clinicians’ hesitancy on PG adoption who identified insufficient education/training, lack of clinical support, test turnaround time and cost as barriers to adoption. CONCLUSION Our dichotomous findings between the perspectives of our patient and clinician cohorts suggest the uptake of PG is likely to be driven by patients and clinicians need to be prepared to provide information and guidance to their patients.
{"title":"Clinical utilities and end-user experience of pharmacogenomics: 39 mo of clinical implementation experience in an Australian hospital setting","authors":"Ros Moxham, Andrew Tjokrowidjaja, Sophie Devery, Renée Smyth, Alison McLean, Darren M Roberts, Kathy H C Wu","doi":"10.5496/wjmg.v11.i4.39","DOIUrl":"https://doi.org/10.5496/wjmg.v11.i4.39","url":null,"abstract":"BACKGROUND\u0000 Pharmacogenomics (PG) testing is under-utilised in Australia. Our research provides Australia-specific data on the perspectives of patients who have had PG testing and those of the clinicians involved in their care, with the aim to inform wider adoption of PG into routine clinical practice.\u0000 AIM\u0000 To investigate the frequency of actionable drug gene interactions and assess the perceived utility of PG among patients and clinicians\u0000 METHODS\u0000 We conducted a retrospective audit of PG undertaken by 100 patients at an Australian public hospital genetics service from 2018 to 2021. Via electronic surveys we compared and contrasted the experience, understanding and usage of results between these patients and their clinicians.\u0000 RESULTS\u0000 Of 100 patients who had PG, 84% were taking prescription medications, of which 67% were taking medications with actionable drug-gene interactions. Twenty-five out of 81 invited patients and 17 out of 89 invited clinicians completed the surveys. Sixty-eight percent of patients understood their PG results and 48% had medications changed following testing. Paired patient-clinician surveys showed patient-perceived utility and experience was positive, contrasting their clinicians’ hesitancy on PG adoption who identified insufficient education/training, lack of clinical support, test turnaround time and cost as barriers to adoption.\u0000 CONCLUSION\u0000 Our dichotomous findings between the perspectives of our patient and clinician cohorts suggest the uptake of PG is likely to be driven by patients and clinicians need to be prepared to provide information and guidance to their patients.","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138955153","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}
Interleukin-2 (IL-2) is an important cytokine that plays a key role in the immune response. The IL-2 receptor (IL-2R) is composed of three subunits, alpha, beta, and gamma, with the alpha subunit having the highest affinity for IL-2. Several studies reported that immune dysregulation of IL-2 may cause tissue injury as well as damage leading to the pathogenesis of various autoimmune diseases such as acute necrotizing vasculitis in systemic lupus erythematosus (SLE), inflammatory synovitis in rheumatoid arthritis (RA), salivary and lacrimal gland dys-function in Sjogren syndrome (SS), obliterative vasculopathy fibrosis in systemic sclerosis (SSc), and inflammatory demyelination in multiple sclerosis (MS). The aim of this review paper was to examine the role of IL-2/IL-2R in various autoimmune disorders, taking into account recent advancements and discoveries, gaps in the current literature, ongoing debates, and potential avenues for future research. The focus of this review is on systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, sjogren syndrome, and multiple sclerosis, which are all linked to the malfunctioning of IL-2/IL-2R. In genetic studies, gene polymorphisms of IL-2 such as IL-2 330/T, IL-2 330/G, and rs2069763 are involved in increasing the risk of SLE. Furthermore, genetic associations of IL-2/IL-2R such as rs791588, rs2281089, rs2104286, rs11594656, and rs35285258 are significantly associated with RA susceptibility. The IL-2 polymorphism including rs2069762A, rs6822844T, rs6835457G, and rs907715T are significant connections with systemic sclerosis. In addition, rs2104286 (IL-2), rs11594656 (IL-2RA), rs35285258 (IL-2RB) gene polymorphism significant increases the risk of multiple sclerosis. In therapeutic approaches, low-dose IL-2 therapy could regulate Tfr and Tfh cells, resulting in a reduction in disease activity in the SLE patients. In addition, elevated sIL-2R levels in the peripheral blood of SLE patients could be linked to an immunoregulatory imbalance, which may contribute to the onset and progression of SLE. Consequently, sIL-2R could potentially be a target for future SLE therapy. Moreover, Low dose-IL2 was well-tolerated, and low levels of Treg and high levels of IL-21 were associated with positive responses to Ld-IL2 suggested to be a safe and effective treatment for RA. Additionally, low-dose IL-2 treatment improves the exocrine glands' ability to secrete saliva in SS-affected mice. Whereas, Basiliximab targets the alpha chain of the IL-2 receptor suggested as a potential treatment for SSc. Also, pre-and post-treatment with Tregs, MDSCs, and IL-2 may have the potential to prevent EAE induction in patients with MS. It is suggested that further studies should be conducted on IL-2 polymorphism in Sjogren syndrome.
{"title":"Role of IL-2/IL-2 receptor in pathogenesis of autoimmune disorders: Genetic and therapeutic aspects","authors":"Sana Rafaqat, Saira Rafaqat","doi":"10.5496/wjmg.v11.i3.28","DOIUrl":"https://doi.org/10.5496/wjmg.v11.i3.28","url":null,"abstract":"Interleukin-2 (IL-2) is an important cytokine that plays a key role in the immune response. The IL-2 receptor (IL-2R) is composed of three subunits, alpha, beta, and gamma, with the alpha subunit having the highest affinity for IL-2. Several studies reported that immune dysregulation of IL-2 may cause tissue injury as well as damage leading to the pathogenesis of various autoimmune diseases such as acute necrotizing vasculitis in systemic lupus erythematosus (SLE), inflammatory synovitis in rheumatoid arthritis (RA), salivary and lacrimal gland dys-function in Sjogren syndrome (SS), obliterative vasculopathy fibrosis in systemic sclerosis (SSc), and inflammatory demyelination in multiple sclerosis (MS). The aim of this review paper was to examine the role of IL-2/IL-2R in various autoimmune disorders, taking into account recent advancements and discoveries, gaps in the current literature, ongoing debates, and potential avenues for future research. The focus of this review is on systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, sjogren syndrome, and multiple sclerosis, which are all linked to the malfunctioning of IL-2/IL-2R. In genetic studies, gene polymorphisms of IL-2 such as IL-2 330/T, IL-2 330/G, and rs2069763 are involved in increasing the risk of SLE. Furthermore, genetic associations of IL-2/IL-2R such as rs791588, rs2281089, rs2104286, rs11594656, and rs35285258 are significantly associated with RA susceptibility. The IL-2 polymorphism including rs2069762A, rs6822844T, rs6835457G, and rs907715T are significant connections with systemic sclerosis. In addition, rs2104286 (IL-2), rs11594656 (IL-2RA), rs35285258 (IL-2RB) gene polymorphism significant increases the risk of multiple sclerosis. In therapeutic approaches, low-dose IL-2 therapy could regulate Tfr and Tfh cells, resulting in a reduction in disease activity in the SLE patients. In addition, elevated sIL-2R levels in the peripheral blood of SLE patients could be linked to an immunoregulatory imbalance, which may contribute to the onset and progression of SLE. Consequently, sIL-2R could potentially be a target for future SLE therapy. Moreover, Low dose-IL2 was well-tolerated, and low levels of Treg and high levels of IL-21 were associated with positive responses to Ld-IL2 suggested to be a safe and effective treatment for RA. Additionally, low-dose IL-2 treatment improves the exocrine glands' ability to secrete saliva in SS-affected mice. Whereas, Basiliximab targets the alpha chain of the IL-2 receptor suggested as a potential treatment for SSc. Also, pre-and post-treatment with Tregs, MDSCs, and IL-2 may have the potential to prevent EAE induction in patients with MS. It is suggested that further studies should be conducted on IL-2 polymorphism in Sjogren syndrome.","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45708772","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}
{"title":"Genome-wide associations, polygenic risk, and Mendelian randomization reveal limited interactions between John Henryism and cynicism","authors":"Richard R Chapleau","doi":"10.5496/wjmg.v11.i2.8","DOIUrl":"https://doi.org/10.5496/wjmg.v11.i2.8","url":null,"abstract":"","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135912583","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}
R. Franceschi, F. Rivieri, A. Novelli, Daniele Ferretti, A. Anesi, M. Soffiati, Giulia Porretti, Evelina Maines, M. Mucciolo, G. Radetti
{"title":"Mosaicism of a novel variant in the ANKRD11 gene in a child with a mild KBG phenotype: A case report","authors":"R. Franceschi, F. Rivieri, A. Novelli, Daniele Ferretti, A. Anesi, M. Soffiati, Giulia Porretti, Evelina Maines, M. Mucciolo, G. Radetti","doi":"10.5496/wjmg.v11.i2.21","DOIUrl":"https://doi.org/10.5496/wjmg.v11.i2.21","url":null,"abstract":"","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46074007","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}
{"title":"Phenotypic and cytogenetic features of an Iranian child with tetrasomy 18p syndrome: A case report","authors":"S. Esmaeili, C. Xian","doi":"10.5496/wjmg.v11.i1.1","DOIUrl":"https://doi.org/10.5496/wjmg.v11.i1.1","url":null,"abstract":"","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43473155","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 : 2022-12-14DOI: 10.1101/2022.12.12.22283345
R. Chapleau
Chronic occupational stress and an individual's reaction to that stress often lead to burnout syndrome. We sought to use genetics to evaluate what, if any, interactions exist between John Henryism (JH) and cynicism in hopes of clarifying holistic risk factors of burnout syndrome. We performed genome-wide association studies in a discover phase with 1,852 samples and validated associations in a replication phase of 465 samples, both from the CARDIA study, and used supervised machine learning to developing genetic risk algorithms. We identified 933 genetic associations and developed a classification algorithm for high cynicism using machine learning with areas under the receiver operator characteristics curve greater than 0.7. We found significant genetic components to these traits but no evidence of an interaction between JH and cynicism, so while there may be a genetic risk component, JH does not appear to contribute to burnout risk.
{"title":"Genome-wide Associations, Polygenic Risk, and Mendelian Randomization Reveal Limited Interactions between John Henryism and Cynicism","authors":"R. Chapleau","doi":"10.1101/2022.12.12.22283345","DOIUrl":"https://doi.org/10.1101/2022.12.12.22283345","url":null,"abstract":"Chronic occupational stress and an individual's reaction to that stress often lead to burnout syndrome. We sought to use genetics to evaluate what, if any, interactions exist between John Henryism (JH) and cynicism in hopes of clarifying holistic risk factors of burnout syndrome. We performed genome-wide association studies in a discover phase with 1,852 samples and validated associations in a replication phase of 465 samples, both from the CARDIA study, and used supervised machine learning to developing genetic risk algorithms. We identified 933 genetic associations and developed a classification algorithm for high cynicism using machine learning with areas under the receiver operator characteristics curve greater than 0.7. We found significant genetic components to these traits but no evidence of an interaction between JH and cynicism, so while there may be a genetic risk component, JH does not appear to contribute to burnout risk.","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47836184","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}
T. Yahaya, Danlami M Bashar, E. Oladele, Ja'afar Umar, D. Anyebe, A. Izuafa
{"title":"Epigenetics in the etiology and management of infertility","authors":"T. Yahaya, Danlami M Bashar, E. Oladele, Ja'afar Umar, D. Anyebe, A. Izuafa","doi":"10.5496/wjmg.v10.i2.7","DOIUrl":"https://doi.org/10.5496/wjmg.v10.i2.7","url":null,"abstract":"","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49064203","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}
BACKGROUND Celiac sprue, or celiac disease, is a relatively common disease whereby many are unaware that they have it. It often manifests with symptoms outside of the digestive system. Many health care providers are unaware of the wide variety of symptoms of celiac disease as well as diseases that are associated with it, often delaying diagnosis and treatment. CASE SUMMARY The following case indicates an otherwise healthy 20-year-old female who presents with a variety of symptoms and is ultimately diagnosed with shingles, infectious mononucleosis, and celiac disease CONCLUSION Although it is known that risk-factors are genetic as well as environmental, much more research is needed to better understand the relationship of potential causes. In addition, continuing education is needed in health care so that more practitioners better understand celiac disease.
{"title":"Celiac sprue - a cryptic disease: A case report","authors":"L. Maness","doi":"10.5496/wjmg.v10.i1.1","DOIUrl":"https://doi.org/10.5496/wjmg.v10.i1.1","url":null,"abstract":"BACKGROUND Celiac sprue, or celiac disease, is a relatively common disease whereby many are unaware that they have it. It often manifests with symptoms outside of the digestive system. Many health care providers are unaware of the wide variety of symptoms of celiac disease as well as diseases that are associated with it, often delaying diagnosis and treatment. CASE SUMMARY The following case indicates an otherwise healthy 20-year-old female who presents with a variety of symptoms and is ultimately diagnosed with shingles, infectious mononucleosis, and celiac disease CONCLUSION Although it is known that risk-factors are genetic as well as environmental, much more research is needed to better understand the relationship of potential causes. In addition, continuing education is needed in health care so that more practitioners better understand celiac disease.","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41683184","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}
We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud's phenomenon, and hypermobility. She was found to have a 6074A > T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classified as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient's symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome (EDS). At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X deficiency, but the variant identified in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A > T nucleotide transition in the TNXB gene may be classified as disease-causing for EDS due to tenascin-X deficiency.
{"title":"Mutation in <i>TNXB</i> gene causes moderate to severe Ehlers-Danlos syndrome.","authors":"Carolyn S Kaufman, Merlin G Butler","doi":"10.5496/wjmg.v6.i2.17","DOIUrl":"https://doi.org/10.5496/wjmg.v6.i2.17","url":null,"abstract":"<p><p>We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud's phenomenon, and hypermobility. She was found to have a 6074A > T nucleotide transition in the <i>TNXB</i> gene causing an amino acid protein change at Asp2025Val classified as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient's symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome (EDS). At the time of writing, a few mutations in the <i>TNXB</i> gene have been recognized as pathogenic causing EDS due to tenascin-X deficiency, but the variant identified in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A > T nucleotide transition in the <i>TNXB</i> gene may be classified as disease-causing for EDS due to tenascin-X deficiency.</p>","PeriodicalId":70632,"journal":{"name":"世界遗传转化学杂志(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/60/nihms814447.PMC5363719.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34857403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：