PMID- 34945057
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211228
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 10
IP  - 24
DP  - 2021 Dec 9
TI  - Association of Genes of the NO Pathway with Altitude Disease and Hypoxic 
      Pulmonary Hypertension.
LID - 10.3390/jcm10245761 [doi]
LID - 5761
AB  - Chronic intermittent hypoxia leads to high-altitude pulmonary hypertension, which 
      is associated with high asymmetric dimethylarginine (ADMA), an endogenous 
      inhibitor of nitric oxide synthesis. Therefore, we aimed to understand the 
      relation of single nucleotide polymorphisms in this pathway to high-altitude 
      pulmonary hypertension (HAPH). We genotyped 69 healthy male Chileans subjected to 
      chronic intermittent hypoxia. Acclimatization to altitude was determined using 
      the Lake Louise Score and the presence of acute mountain sickness. 
      Echocardiography was performed after six months in 24 individuals to estimate 
      pulmonary arterial pressure. The minor allele of dimethylarginine 
      dimethylaminohydrolase (DDAH)1 rs233112 was associated with high-baseline plasma 
      ADMA concentration, while individuals homozygous for the major allele of DDAH2 
      rs805304 had a significantly greater increase in ADMA during chronic intermittent 
      hypoxia. The major allele of alanine glyoxylate aminotransferase-2 (AGXT2) 
      rs37369 was associated with a greater reduction of plasma symmetric 
      dimethylarginine (SDMA). Several genes were associated with high-altitude 
      pulmonary hypertension, and the nitric oxide synthase (NOS)3 and DDAH2 genes were 
      related to acute mountain sickness. In conclusion, DDAH1 determines baseline 
      plasma ADMA, while DDAH2 modulates ADMA increase in hypoxia. AGXT2 may be 
      up-regulated in hypoxia. Genomic variation in the dimethylarginine pathway 
      affects the development of HAPH and altitude acclimatization.
FAU - Hannemann, Juliane
AU  - Hannemann J
AUID- ORCID: 0000-0003-3499-4827
AD  - Institute of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, 20246 Hamburg, Germany.
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and Its Health Sequelae, 20246 Hamburg, Germany and Iquique 1100000, Chile.
FAU - Siques, Patricia
AU  - Siques P
AUID- ORCID: 0000-0002-4963-195X
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and Its Health Sequelae, 20246 Hamburg, Germany and Iquique 1100000, Chile.
AD  - Institute of Health Studies, Universidad Arturo Prat, Iquique 1100000, Chile.
FAU - Schmidt-Hutten, Lena
AU  - Schmidt-Hutten L
AD  - Institute of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, 20246 Hamburg, Germany.
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and Its Health Sequelae, 20246 Hamburg, Germany and Iquique 1100000, Chile.
FAU - Zummack, Julia
AU  - Zummack J
AUID- ORCID: 0000-0002-5226-3393
AD  - Institute of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, 20246 Hamburg, Germany.
FAU - Brito, Julio
AU  - Brito J
AUID- ORCID: 0000-0002-0050-8774
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and Its Health Sequelae, 20246 Hamburg, Germany and Iquique 1100000, Chile.
AD  - Institute of Health Studies, Universidad Arturo Prat, Iquique 1100000, Chile.
FAU - Boger, Rainer
AU  - Boger R
AUID- ORCID: 0000-0003-3770-5357
AD  - Institute of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, 20246 Hamburg, Germany.
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and Its Health Sequelae, 20246 Hamburg, Germany and Iquique 1100000, Chile.
LA  - eng
GR  - 01DN17046/Federal Ministry of Education and Research/
GR  - NA/Georg & Jurgen Rickertsen Foundation/
GR  - 02/96/Werner Otto Stiftung/
GR  - 400187737/FIC-GORE TARAPACA/
PT  - Journal Article
DEP - 20211209
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC8704804
OTO - NOTNLM
OT  - DDAH
OT  - arginase
OT  - asymmetric dimethylarginine (ADMA)
OT  - chronic intermittent hypoxia
OT  - echocardiography
OT  - high altitude
OT  - nitric oxide synthase
OT  - single nucleotide polymorphisms
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2021/12/25 06:00
MHDA- 2021/12/25 06:01
PMCR- 2021/12/09
CRDT- 2021/12/24 01:07
PHST- 2021/11/22 00:00 [received]
PHST- 2021/12/06 00:00 [revised]
PHST- 2021/12/07 00:00 [accepted]
PHST- 2021/12/24 01:07 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2021/12/25 06:01 [medline]
PHST- 2021/12/09 00:00 [pmc-release]
AID - jcm10245761 [pii]
AID - jcm-10-05761 [pii]
AID - 10.3390/jcm10245761 [doi]
PST - epublish
SO  - J Clin Med. 2021 Dec 9;10(24):5761. doi: 10.3390/jcm10245761.