The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

油症息者の口腔内粘膜と歯牙所見

特集号 油症とPCB及びダイオキシン関連化合物 研究報告第20集 責任編集者 古江増隆The Twentieth Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka Furue油症発症後約35年が経過しようとしている.油症発症後早期においては,体調不良,食欲不振や眼脂過多等の所見に加えて,座瘡様皮疹や色素沈着が顕著に認められた.歯科領域においても,歯根形態異常や永久歯萌出遅延が観察されている.時間の経過とともに,口腔内色素沈着の色調は徐々に薄くなってきているが,依然として被検者の約半数に色素沈着が認められている.本論文では,口腔内疾患,特に色素沈着発現の経年的推移ならびにPCB等とこれら疾患との関連について述べてみたい

油症息者の口腔内粘膜と歯牙所見

油症発症後約35年が経過しようとしている.油症発症後早期においては,体調不良,食欲不振や眼脂過多等の所見に加えて,座瘡様皮疹や色素沈着が顕著に認められた.歯科領域においても,歯根形態異常や永久歯萌出遅延が観察されている.時間の経過とともに,口腔内色素沈着の色調は徐々に薄くなってきているが,依然として被検者の約半数に色素沈着が認められている.本論文では,口腔内疾患,特に色素沈着発現の経年的推移ならびにPCB等とこれら疾患との関連について述べてみたい.特集号 油症とPCB及びダイオキシン関連化合物 研究報告第20集 責任編集者 古江増隆The Twentieth Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka Furu

2002年度における油症患者の歯周疾患ならびに口腔内色素沈着の疫学的調査

特集号 油症とPCB及びダイオキシン関連化合物 研究報告第19集 責任編集者 古江増隆The Nineteenth Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka FurueAn epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho. The results obtained were as follows. 1)95 patients out of 110 patients, who were examined periodontal pocket depth using Ramfjord\u27 methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 276 teeth out of a total 495 examined teeth showed periodontal pockets with more than 3 mm depth. However, the ratio of the teeth with periodontal pockets deeper than 4mm to total examined teeth in each age fell to less than 25%. 2)Oral pigmentation was observed in 75 patients out of 121 patien ts with Yusho. In this examination, gingival pigmentation was most predominant among oral pigmentation. It is of particular interest that severe pigmentation tended to be observed at a much higher frequency in younger patients with Yusho. Taken these findings into consid eration, it was suggested that PCBs and related compounds might play an important role in the development of both periodontal diseases and oral pigmentation.油症患者における歯周疾患や口腔内色素沈着の罹患状況の経年的変化を把握するために, 平成14年度の福岡県油症一斉検診を受診した油症認定患者を対象に口腔内診査を行った. 1)深さ3mm以上の歯周ポケットを1歯でも有している患者は95名(86.4%)で, また3mm以上の歯周ポケットを有する歯牙は495の総被検歯のうち276歯(55.8%)といずれも高い割合を示した. 2)121名の油症認定患者のうち75名に口腔内色素沈着がみられた. 部位としては歯肉にみられるものがほとんどであった. 加齢と共に色素沈着の発現率は低下しており, 加えて色素沈着の程度も若年者に比べて高齢者の方が軽微であった. 以上の結果から, 油症患者においては辺縁性歯肉炎および口腔内色素沈着の罹患率が依然として高く, 機序については不明だがPCBsやその代謝産物がこれらの病変の発症や進展に関与していると考えられる

An Epidemiologic Examination on the Prevalence of the Periodontal Diseases and Oral Pigmentation in Yusho Patients in 2006

特集号 油症とPCB及びダイオキシン関連化合物 研究報告第21集 責任編集者 古江増隆The Twenty-first Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka FurueAn epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho in 2006. The results obtained were as follows. 1)98patients out of106patients with Yusho,who were measured periodontal pocket depth according to Ramfjord’methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 343 teeth out of a total 494 examined teeth showed periodontal pocket with more than 3 mm depth. 2)Oral pigmentation was observed in 61 patients out of 116 patients with Yusho. In this study, gingival pigmentation was most predominant among oral pigmentation. The prevalence of oral pigmentation in male patients seemed to be somewhat higher than that in female patients. In addition, this examination revealed that the patients below the age of sixty had a high prevalence of oral pigmentation. These results indicated that PCB-related compounds may be responsible for the higher prevalence of both periodontal diseases and oral pigmentation

An Epidemiologic Examination on the Prevalence of the Periodontal Diseases and Oral Pigmentation in Yusho Patients in 2002

An epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho. The results obtained were as follows. 1)95 patients out of 110 patients, who were examined periodontal pocket depth using Ramfjord' methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 276 teeth out of a total 495 examined teeth showed periodontal pockets with more than 3 mm depth. However, the ratio of the teeth with periodontal pockets deeper than 4mm to total examined teeth in each age fell to less than 25%. 2)Oral pigmentation was observed in 75 patients out of 121 patien ts with Yusho. In this examination, gingival pigmentation was most predominant among oral pigmentation. It is of particular interest that severe pigmentation tended to be observed at a much higher frequency in younger patients with Yusho. Taken these findings into consid eration, it was suggested that PCBs and related compounds might play an important role in the development of both periodontal diseases and oral pigmentation.油症患者における歯周疾患や口腔内色素沈着の罹患状況の経年的変化を把握するために, 平成14年度の福岡県油症一斉検診を受診した油症認定患者を対象に口腔内診査を行った. 1)深さ3mm以上の歯周ポケットを1歯でも有している患者は95名(86.4%)で, また3mm以上の歯周ポケットを有する歯牙は495の総被検歯のうち276歯(55.8%)といずれも高い割合を示した. 2)121名の油症認定患者のうち75名に口腔内色素沈着がみられた. 部位としては歯肉にみられるものがほとんどであった. 加齢と共に色素沈着の発現率は低下しており, 加えて色素沈着の程度も若年者に比べて高齢者の方が軽微であった. 以上の結果から, 油症患者においては辺縁性歯肉炎および口腔内色素沈着の罹患率が依然として高く, 機序については不明だがPCBsやその代謝産物がこれらの病変の発症や進展に関与していると考えられる.特集号 油症とPCB及びダイオキシン関連化合物 研究報告第19集 責任編集者 古江増隆The Nineteenth Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka Furu

An Epidemiologic Examination on the Prevalence of the Periodontal Diseases and Oral Pigmentation in Yusho Patients in 2008

特集号 油症とPCB及びダイオキシン関連化合物 研究報告第22集 責任編集者 古江増隆The Twenty-second Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka FurueAn epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho in 2008. The results obtained were as follows. 1) Yusho patients complained of tooth pain and periodontal diseases such as gingival swelling, gingival bleeding, but not of oral pigmentation. 2) 116 patients out of 148 patients with Yusho, who were measured periodontal pocket depth according to Ramfjord\u27 methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 399 teeth out of a total 710 examined teeth showed a periodontal pocket with more than 3 mm in depth. However, it was determined that 74 teeth had a periodontal pocket deeper than 4 mm. 3) Oral pigmentation was observed in 91 patients out of 155 patients with Yusho. In this study, gingival pigmentation was most predominant among oral pigmentation. The prevalence of oral pigmentation in male patients seemed to be somewhat higher than that in female patients. In addition, the prevalence of oral pigmentation tended to be higher in younger patients than in elder patients. Pigmentation of the buccal mucosa, lip or palate, however, was observed only in patients beyond the age of fifty. These results indicated that PCB-related compounds may be responsible for the higher prevalence of both periodontal diseases and oral pigmentation

An Epidemiologic Examination on the Prevalence of the Periodontal Diseases and Oral Pigmentation in Yusho Patients in 2010

特集号 油症とPCB及びダイキシン関連化合物 研究報告 第23集 責任編集者 古江増隆The Twenty-third Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Furue MasutakaAn epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho in 2010. The results obtained were as follows. 1) Yusho patients complained of tooth pain and periodontal diseases such as gingival swelling, but not of oral pigmentation. 2) 104 patients out of 117 patients with Yusho, who were measured periodontal pocket depth according to Ramfjord\u27 methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 314 teeth out of a total 551 examined teeth showed a periodontal pocket with more than 3 mm in depth. However, it was determined that 57 teeth had a periodontal pocket deeper than 4 mm. 3) Oral pigmentation was observed in 63 patients out of 122 patients with Yusho. In this study, gingival pigmentation was most predominant among oral pigmentation. The prevalence of oral pigmentation in male patients seemed to be somewhat higher than that in female patients. In addition, the prevalence of oral pigmentation tended to be higher in patients under seventy years old than patients beyond the age of seventy. These results indicated that PCB-related compounds may be responsible for the higher prevalence of both periodontal diseases and oral pigmentation.我々は，年一回行われる福岡県油症一斉検診の場において，油症患者の口腔内所見について追跡調査を行っている．その結果，油症発症後早期に認められた所見のうち歯根形態異常や永久歯萌出遅延はほとんど認められなくなってきているが，依然として被検者の約半数に口腔内色素沈着が認められることや歯周疾患罹患率が高いことを報告してきた．そこで，平成22年度の福岡県における油症患者の一斉検診時の結果を基に，口腔内疾患特に歯周疾患や口腔内色素沈着の罹患状況について報告するとともに，平成21年度のデーターと比較しこれら疾患の経年的変化についても検討を行った

油症患者における歯周疾患ならびに口腔内色素沈着の疫学的調査（第八報）

An epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho in 2010. The results obtained were as follows. 1) Yusho patients complained of tooth pain and periodontal diseases such as gingival swelling, but not of oral pigmentation. 2) 104 patients out of 117 patients with Yusho, who were measured periodontal pocket depth according to Ramfjord' methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 314 teeth out of a total 551 examined teeth showed a periodontal pocket with more than 3 mm in depth. However, it was determined that 57 teeth had a periodontal pocket deeper than 4 mm. 3) Oral pigmentation was observed in 63 patients out of 122 patients with Yusho. In this study, gingival pigmentation was most predominant among oral pigmentation. The prevalence of oral pigmentation in male patients seemed to be somewhat higher than that in female patients. In addition, the prevalence of oral pigmentation tended to be higher in patients under seventy years old than patients beyond the age of seventy. These results indicated that PCB-related compounds may be responsible for the higher prevalence of both periodontal diseases and oral pigmentation.我々は，年一回行われる福岡県油症一斉検診の場において，油症患者の口腔内所見について追跡調査を行っている．その結果，油症発症後早期に認められた所見のうち歯根形態異常や永久歯萌出遅延はほとんど認められなくなってきているが，依然として被検者の約半数に口腔内色素沈着が認められることや歯周疾患罹患率が高いことを報告してきた．そこで，平成22年度の福岡県における油症患者の一斉検診時の結果を基に，口腔内疾患特に歯周疾患や口腔内色素沈着の罹患状況について報告するとともに，平成21年度のデーターと比較しこれら疾患の経年的変化についても検討を行った．特集号 油症とPCB及びダイキシン関連化合物 研究報告 第23集 責任編集者 古江増隆The Twenty-third Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Furue Masutak