PMID- 33103541
OWN - NLM
STAT- MEDLINE
DCOM- 20210326
LR  - 20231110
IS  - 2047-9980 (Electronic)
IS  - 2047-9980 (Linking)
VI  - 9
IP  - 21
DP  - 2020 Nov 3
TI  - Identification of the Novel Variants in Patients With Chronic Thromboembolic 
      Pulmonary Hypertension.
PG  - e015902
LID - 10.1161/JAHA.120.015902 [doi]
LID - e015902
AB  - Background Although chronic thromboembolic pulmonary hypertension (CTEPH) and 
      acute pulmonary embolism (APE) share some clinical manifestations, a limited 
      proportion of patients with CTEPH have a history of APE. Moreover, in 
      histopathologic studies, it has been revealed that pulmonary vasculature lesions 
      similar to pulmonary arterial hypertension existed in patients with CTEPH. Thus, 
      it remains unknown whether these 3 disorders also share genetic backgrounds. 
      Methods and Results Whole exome screening was performed with DNA isolated from 51 
      unrelated patients with CTEPH of Japanese ancestry. The frequency of genetic 
      variants associated with pulmonary arterial hypertension or APE in patients with 
      CTEPH was compared with those in the integrative Japanese Genome Variation 
      Database 3.5KJPN. Whole exome screening analysis showed 17 049 nonsynonymous 
      variants in patients with CTEPH. Although we found 6 nonsynonymous variants that 
      are associated with APE in patients with CTEPH, there was no nonsynonymous 
      variant associated with pulmonary arterial hypertension. Patients with CTEPH with 
      a history of APE had nonsynonymous variants of F5, which encodes factor V. In 
      contrast, patients with CTEPH without a history of APE had a nonsynonymous 
      variant of THBD, which encodes thrombomodulin. Moreover, thrombin-activatable 
      fibrinolysis inhibitor, which is one of the pathogenic proteins in CTEPH, was 
      significantly more activated in those who had the variants of THBD compared with 
      those without it. Conclusions These results provide the first evidence that 
      patients with CTEPH have some variants associated with APE, regardless of the 
      presence or absence of a history of APE. Furthermore, the variants might be 
      different between patients with CTEPH with and without a history of APE.
FAU - Yaoita, Nobuhiro
AU  - Yaoita N
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Satoh, Kimio
AU  - Satoh K
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Satoh, Taijyu
AU  - Satoh T
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Shimizu, Toru
AU  - Shimizu T
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Saito, Sakae
AU  - Saito S
AD  - Department of Integrative Genomics Tohoku Medical Megabank Organization Tohoku 
      University Sendai Japan.
FAU - Sugimura, Koichiro
AU  - Sugimura K
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Tatebe, Shunsuke
AU  - Tatebe S
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Yamamoto, Saori
AU  - Yamamoto S
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Aoki, Tatsuo
AU  - Aoki T
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Kikuchi, Nobuhiro
AU  - Kikuchi N
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Kurosawa, Ryo
AU  - Kurosawa R
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Miyata, Satoshi
AU  - Miyata S
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
FAU - Nagasaki, Masao
AU  - Nagasaki M
AD  - Department of Integrative Genomics Tohoku Medical Megabank Organization Tohoku 
      University Sendai Japan.
FAU - Yasuda, Jun
AU  - Yasuda J
AD  - Department of Integrative Genomics Tohoku Medical Megabank Organization Tohoku 
      University Sendai Japan.
FAU - Shimokawa, Hiroaki
AU  - Shimokawa H
AD  - Department of Cardiovascular Medicine Tohoku University Graduate School of 
      Medicine Sendai Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201024
PL  - England
TA  - J Am Heart Assoc
JT  - Journal of the American Heart Association
JID - 101580524
RN  - 0 (THBD protein, human)
RN  - 0 (Thrombomodulin)
RN  - 9001-24-5 (Factor V)
RN  - EC 3.4.17.20 (CPB2 protein, human)
RN  - EC 3.4.17.20 (Carboxypeptidase B2)
SB  - IM
MH  - Acute Disease
MH  - Aged
MH  - Aged, 80 and over
MH  - Asian People/*genetics
MH  - Carboxypeptidase B2/genetics
MH  - Chronic Disease
MH  - Factor V/genetics
MH  - Female
MH  - Gene Frequency/genetics
MH  - Genetic Variation/*genetics
MH  - Humans
MH  - Hypertension, Pulmonary/*complications/*genetics
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Pulmonary Embolism/*complications/*genetics
MH  - Thrombomodulin/genetics
MH  - Exome Sequencing
PMC - PMC7763425
OTO - NOTNLM
OT  - chronic thromboembolic pulmonary hypertension
OT  - gene variants
OT  - pulmonary hypertension
COIS- None.
EDAT- 2020/10/27 06:00
MHDA- 2021/03/27 06:00
PMCR- 2020/11/03
CRDT- 2020/10/26 08:42
PHST- 2020/10/27 06:00 [pubmed]
PHST- 2021/03/27 06:00 [medline]
PHST- 2020/10/26 08:42 [entrez]
PHST- 2020/11/03 00:00 [pmc-release]
AID - JAH35583 [pii]
AID - 10.1161/JAHA.120.015902 [doi]
PST - ppublish
SO  - J Am Heart Assoc. 2020 Nov 3;9(21):e015902. doi: 10.1161/JAHA.120.015902. Epub 
      2020 Oct 24.