Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People

IMPORTANCE:. The pathology caused by the coronavirus disease 2019 is mediated by host-mediated lung inflammation, driving severity, and mortality. Polymorphisms in genes encoding host inflammation and immune-related molecules may be associated with the development of serious pathologies, and identif...

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Autores principales:	Naoki Tanimine, MD, PhD, Daisuke Takei, MD, Naohumi Tsukiyama, MD, Hisaaki Yoshinaka, MD, Yuki Takemoto, MD, Yuka Tanaka, PhD, Tsuyoshi Kobayashi, MD, PhD, Kazuaki Tanabe, MD, PhD, Nobuhisa Ishikawa, MD, PhD, Yoshihiro Kitahara, MD, PhD, Mafumi Okimoto, MD, Nobuaki Shime, MD, PhD, Hiroki Ohge, MD, PhD, Aya Sugiyama, MD, PhD, Tomoyuki Akita, PhD, Junko Tanaka, PhD, Hideki Ohdan, MD, PhD
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer 2021
Materias:	Medical emergencies. Critical care. Intensive care. First aid RC86-88.9
Acceso en línea:	https://doaj.org/article/12e1fdf3a6344ad6aff40336c40788b1
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spelling	oai:doaj.org-article:12e1fdf3a6344ad6aff40336c40788b12021-11-25T07:56:59ZIdentification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People2639-802810.1097/CCE.0000000000000576https://doaj.org/article/12e1fdf3a6344ad6aff40336c40788b12021-11-01T00:00:00Zhttp://journals.lww.com/10.1097/CCE.0000000000000576https://doaj.org/toc/2639-8028IMPORTANCE:. The pathology caused by the coronavirus disease 2019 is mediated by host-mediated lung inflammation, driving severity, and mortality. Polymorphisms in genes encoding host inflammation and immune-related molecules may be associated with the development of serious pathologies, and identifying such gene polymorphisms may lead to the identification of therapeutic targets. OBJECTIVES:. We attempted to identify aggravation-predicting gene polymorphisms. DESIGN:. We use a candidate gene approach associated with multiple phase pathogenesis in coronavirus disease 2019 patients among a cohort in Hiroshima, a city with a population of 1 million, in Japan. DNA samples from the study populations were genotyped for 34 functional polymorphisms from 14 distinct candidate genes, which encode proteins related to viral cell entry, regulation of viral replication, innate immune modulators, regulatory cytokines, and effector cytokines. SETTING AND PARTICIPANTS:. Three core hospitals providing different services for patients with coronavirus disease 2019 under administrative control. A total of 230 patients with coronavirus disease 2019 were recruited from March 1, 2020, to March 31, 2021. MAIN RESULTS AND MEASUREMENTS:. Among the 14 genes, we found rs1131454 in OAS1 and rs1143627 in IL1B genes as independent genetic factors associated with disease severity (adjusted odds ratio = 7.1 and 4.6 in the dominant model, respectively). Furthermore, we investigated the effect of multiple phase pathogenesis of coronavirus disease 2019 with unbiased multifactor dimensionality reduction analysis and identified a four-gene model with rs1131454 (OAS1), rs1143627 (IL1B), rs2074192 (ACE2), and rs11003125 (MBL). By combining these polygenetic factors with polyclinical factors, including age, sex, higher body mass index, and the presence of diabetes and hypertension, we proposed a composite risk model with a high area under the curve, sensitivity, and probability (0.917, 96.4%, and 74.3%, respectively) in the receiver operating characteristic curve analysis. CONCLUSIONS AND RELEVANCE:. We successfully identified significant genetic factors in OAS1 and IL1B genes using a candidate gene approach study as valuable information for further mechanistic investigation and predictive model building.Naoki Tanimine, MD, PhDDaisuke Takei, MDNaohumi Tsukiyama, MDHisaaki Yoshinaka, MDYuki Takemoto, MDYuka Tanaka, PhDTsuyoshi Kobayashi, MD, PhDKazuaki Tanabe, MD, PhDNobuhisa Ishikawa, MD, PhDYoshihiro Kitahara, MD, PhDMafumi Okimoto, MDNobuaki Shime, MD, PhDHiroki Ohge, MD, PhDAya Sugiyama, MD, PhDTomoyuki Akita, PhDJunko Tanaka, PhDHideki Ohdan, MD, PhDWolters KluwerarticleMedical emergencies. Critical care. Intensive care. First aidRC86-88.9ENCritical Care Explorations, Vol 3, Iss 11, p e0576 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medical emergencies. Critical care. Intensive care. First aid RC86-88.9
spellingShingle	Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 Naoki Tanimine, MD, PhD Daisuke Takei, MD Naohumi Tsukiyama, MD Hisaaki Yoshinaka, MD Yuki Takemoto, MD Yuka Tanaka, PhD Tsuyoshi Kobayashi, MD, PhD Kazuaki Tanabe, MD, PhD Nobuhisa Ishikawa, MD, PhD Yoshihiro Kitahara, MD, PhD Mafumi Okimoto, MD Nobuaki Shime, MD, PhD Hiroki Ohge, MD, PhD Aya Sugiyama, MD, PhD Tomoyuki Akita, PhD Junko Tanaka, PhD Hideki Ohdan, MD, PhD Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People
description	IMPORTANCE:. The pathology caused by the coronavirus disease 2019 is mediated by host-mediated lung inflammation, driving severity, and mortality. Polymorphisms in genes encoding host inflammation and immune-related molecules may be associated with the development of serious pathologies, and identifying such gene polymorphisms may lead to the identification of therapeutic targets. OBJECTIVES:. We attempted to identify aggravation-predicting gene polymorphisms. DESIGN:. We use a candidate gene approach associated with multiple phase pathogenesis in coronavirus disease 2019 patients among a cohort in Hiroshima, a city with a population of 1 million, in Japan. DNA samples from the study populations were genotyped for 34 functional polymorphisms from 14 distinct candidate genes, which encode proteins related to viral cell entry, regulation of viral replication, innate immune modulators, regulatory cytokines, and effector cytokines. SETTING AND PARTICIPANTS:. Three core hospitals providing different services for patients with coronavirus disease 2019 under administrative control. A total of 230 patients with coronavirus disease 2019 were recruited from March 1, 2020, to March 31, 2021. MAIN RESULTS AND MEASUREMENTS:. Among the 14 genes, we found rs1131454 in OAS1 and rs1143627 in IL1B genes as independent genetic factors associated with disease severity (adjusted odds ratio = 7.1 and 4.6 in the dominant model, respectively). Furthermore, we investigated the effect of multiple phase pathogenesis of coronavirus disease 2019 with unbiased multifactor dimensionality reduction analysis and identified a four-gene model with rs1131454 (OAS1), rs1143627 (IL1B), rs2074192 (ACE2), and rs11003125 (MBL). By combining these polygenetic factors with polyclinical factors, including age, sex, higher body mass index, and the presence of diabetes and hypertension, we proposed a composite risk model with a high area under the curve, sensitivity, and probability (0.917, 96.4%, and 74.3%, respectively) in the receiver operating characteristic curve analysis. CONCLUSIONS AND RELEVANCE:. We successfully identified significant genetic factors in OAS1 and IL1B genes using a candidate gene approach study as valuable information for further mechanistic investigation and predictive model building.
format	article
author	Naoki Tanimine, MD, PhD Daisuke Takei, MD Naohumi Tsukiyama, MD Hisaaki Yoshinaka, MD Yuki Takemoto, MD Yuka Tanaka, PhD Tsuyoshi Kobayashi, MD, PhD Kazuaki Tanabe, MD, PhD Nobuhisa Ishikawa, MD, PhD Yoshihiro Kitahara, MD, PhD Mafumi Okimoto, MD Nobuaki Shime, MD, PhD Hiroki Ohge, MD, PhD Aya Sugiyama, MD, PhD Tomoyuki Akita, PhD Junko Tanaka, PhD Hideki Ohdan, MD, PhD
author_facet	Naoki Tanimine, MD, PhD Daisuke Takei, MD Naohumi Tsukiyama, MD Hisaaki Yoshinaka, MD Yuki Takemoto, MD Yuka Tanaka, PhD Tsuyoshi Kobayashi, MD, PhD Kazuaki Tanabe, MD, PhD Nobuhisa Ishikawa, MD, PhD Yoshihiro Kitahara, MD, PhD Mafumi Okimoto, MD Nobuaki Shime, MD, PhD Hiroki Ohge, MD, PhD Aya Sugiyama, MD, PhD Tomoyuki Akita, PhD Junko Tanaka, PhD Hideki Ohdan, MD, PhD
author_sort	Naoki Tanimine, MD, PhD
title	Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People
title_short	Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People
title_full	Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People
title_fullStr	Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People
title_full_unstemmed	Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People
title_sort	identification of aggravation-predicting gene polymorphisms in coronavirus disease 2019 patients using a candidate gene approach associated with multiple phase pathogenesis: a study in a japanese city of 1 million people
publisher	Wolters Kluwer
publishDate	2021
url	https://doaj.org/article/12e1fdf3a6344ad6aff40336c40788b1
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Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People

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