Introduction A previous study of 200,000 exome-sequenced UK Biobank participants to test for association of rare coding variants with hypertension implicated two genes at exome-wide significance, DNMT3A and FES. A total of 42 genes had an uncorrected p value < 0.001. These results were followed up in a larger sample of 470,000 exome-sequenced participants. Methods Weighted burden analysis of rare coding variants in a new sample of 97,050 cases and 172,263 controls was carried out for these 42 genes. Those showing evidence for association were then analysed in the combined sample of 167,127 cases and 302,691 controls. Results The association of DNMT3A and FES with hypertension was replicated in the new sample and they and the previously implicated gene NPR1, which codes for a membrane bound guanylate cyclase, were all exome-wide significant in the combined sample. Also exome-wide significant as risk genes for hypertension were GUCY1A1, ASXL1 and SMAD6, while GUCY1B1 had a nominal p value of < 0.0001. GUCY1A1 and GUCY1B1 code for subunits of a soluble guanylate cyclase. For two genes, DBH, which codes for dopamine beta hydroxylase, and INPPL1, rare coding variants predicted to impair gene function were protective against hypertension, again with exome-wide significance. Conclusion The findings offer new insights into biological risk factors for hypertension which could be the subject of further investigation. In particular, genetic variants predicted to impair the function of either membrane-bound guanylate cyclase, activated by natriuretic peptides, or soluble guanylate cyclase, activated by nitric oxide, increase risk of hypertension. Conversely, variants impairing the function of dopamine beta hydroxylase, responsible for the synthesis of norepinephrine, reduce hypertension risk. This research has been conducted using the UK Biobank Resource.
{"title":"Analysis of rare variants in 470,000 exome-sequenced UK Biobank participants implicates novel genes affecting risk of hypertension","authors":"David Curtis","doi":"10.1159/000535157","DOIUrl":"https://doi.org/10.1159/000535157","url":null,"abstract":"Introduction A previous study of 200,000 exome-sequenced UK Biobank participants to test for association of rare coding variants with hypertension implicated two genes at exome-wide significance, DNMT3A and FES. A total of 42 genes had an uncorrected p value < 0.001. These results were followed up in a larger sample of 470,000 exome-sequenced participants. Methods Weighted burden analysis of rare coding variants in a new sample of 97,050 cases and 172,263 controls was carried out for these 42 genes. Those showing evidence for association were then analysed in the combined sample of 167,127 cases and 302,691 controls. Results The association of DNMT3A and FES with hypertension was replicated in the new sample and they and the previously implicated gene NPR1, which codes for a membrane bound guanylate cyclase, were all exome-wide significant in the combined sample. Also exome-wide significant as risk genes for hypertension were GUCY1A1, ASXL1 and SMAD6, while GUCY1B1 had a nominal p value of < 0.0001. GUCY1A1 and GUCY1B1 code for subunits of a soluble guanylate cyclase. For two genes, DBH, which codes for dopamine beta hydroxylase, and INPPL1, rare coding variants predicted to impair gene function were protective against hypertension, again with exome-wide significance. Conclusion The findings offer new insights into biological risk factors for hypertension which could be the subject of further investigation. In particular, genetic variants predicted to impair the function of either membrane-bound guanylate cyclase, activated by natriuretic peptides, or soluble guanylate cyclase, activated by nitric oxide, increase risk of hypertension. Conversely, variants impairing the function of dopamine beta hydroxylase, responsible for the synthesis of norepinephrine, reduce hypertension risk. This research has been conducted using the UK Biobank Resource.","PeriodicalId":29774,"journal":{"name":"Pulse","volume":"54 20","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136282221","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":"Abstracts book of Pulse of Asia 2023","authors":"","doi":"10.1159/000534378","DOIUrl":"https://doi.org/10.1159/000534378","url":null,"abstract":"","PeriodicalId":29774,"journal":{"name":"Pulse","volume":"66 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134982047","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":"The Pulse of Asia 2022 Tokyo","authors":"","doi":"10.1159/000525603","DOIUrl":"https://doi.org/10.1159/000525603","url":null,"abstract":"None<br />Pulse 2022;10:1–34","PeriodicalId":29774,"journal":{"name":"Pulse","volume":"40 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2022-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138538170","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 : 2018-10-19DOI: 10.3329/pulse.v10i1.38605
MM Rahman, R Rahim, AH Rasel, AS Murad
Background: Chikungunya viral infection in Bangladesh has marked 2017 summer with unprecedented magnitude for the first time. Chikungunya virus (CHIKV) and Dengue virus (DENV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas.These two viruses cause similar clinical presentations, especially in the initial stages of infection. Because the outcomes and management strategies for these two viruses are different, early and accurate diagnosis is imperative. Early diagnosis is also important for surveillance and outbreak control. Objective: As virus isolation is not undergoing in the country and antigen based commercial detection assay is not available for CHIKV we used one step real time reverse transcriptase polymerase chain reaction (RT-PCR) method to detect and discriminate CHIKV and DENV in blood during suspicious clinical symptoms. Results: By this RT-PCR method we have detected 603 cases of CHIKV and 233 cases of DENV and thus facilitated rapid diagnosis and clinical management in the recent CHIKV outbreaks in the country. Conclusion: This is the first report about molecular detection and differentiation of CHIKV and DENV at time of clinical presentation and further show evidence of simultaneous outbreaks of both the viral infections in the country. Pulse Vol.10 January-December 2017 p.6-11
{"title":"Simultaneous Detection and Differentiation of Chikungunya Virus and Dengue Virus in Blood at Clinical Presentation by Real Time RT-PCR","authors":"MM Rahman, R Rahim, AH Rasel, AS Murad","doi":"10.3329/pulse.v10i1.38605","DOIUrl":"https://doi.org/10.3329/pulse.v10i1.38605","url":null,"abstract":"Background: Chikungunya viral infection in Bangladesh has marked 2017 summer with unprecedented magnitude for the first time. Chikungunya virus (CHIKV) and Dengue virus (DENV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas.These two viruses cause similar clinical presentations, especially in the initial stages of infection. Because the outcomes and management strategies for these two viruses are different, early and accurate diagnosis is imperative. Early diagnosis is also important for surveillance and outbreak control. Objective: As virus isolation is not undergoing in the country and antigen based commercial detection assay is not available for CHIKV we used one step real time reverse transcriptase polymerase chain reaction (RT-PCR) method to detect and discriminate CHIKV and DENV in blood during suspicious clinical symptoms. Results: By this RT-PCR method we have detected 603 cases of CHIKV and 233 cases of DENV and thus facilitated rapid diagnosis and clinical management in the recent CHIKV outbreaks in the country. Conclusion: This is the first report about molecular detection and differentiation of CHIKV and DENV at time of clinical presentation and further show evidence of simultaneous outbreaks of both the viral infections in the country. Pulse Vol.10 January-December 2017 p.6-11","PeriodicalId":29774,"journal":{"name":"Pulse","volume":"122 ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2018-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138505779","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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