Linked Life Data

18515178

Source:http://linkedlifedata.com/resource/pubmed/id/18515178

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-8-29
pubmed:abstractText
Guanosine triphosphate cyclohydrolase 1 (GCH1) is the first enzyme in the tetrahydrobiopterin (BH4) biosynthesis, an important co-factor for the formation of nitric oxide, biogenic amines and serotonin. Hereditary diseases such as DOPA-responsive dystonia and atypical phenylketonuria are known to be caused by coding or splice-site mutations in the GCH1 gene, leading mostly to a dominant negative enzyme. However, recent evidence suggests a clinical genetics of GCH1 beyond these hereditary loss-of-function diseases. That is, a non-coding GCH1 haplotype has been associated with reduced pain hypersensitivity and with altered vascular endothelial function. Moreover, the presence of the non-coding c.*243C>T variant in the 3'-untranslated region (3'-UTR) of the GCH1 gene has been associated with mildly increased heart rate and blood pressure. Here, we show that carriers of the pain-protective GCH1 haplotype also carry the c.*243C>T variant and vice versa. We thus demonstrate that apart from the coding or splice-site variants causing DOPA-responsive dystonia and atypical phenylketonuria, there is a common clinically relevant GCH1 genetics that is so far known to be related to unfavorable changes of endothelial function and a reduced risk for chronic pain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
659
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-201
pubmed:meshHeading
pubmed:articleTitle
Clinical genetics of functionally mild non-coding GTP cyclohydrolase 1 (GCH1) polymorphisms modulating pain and cardiovascular risk.
pubmed:affiliation
pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Theodor Stern Kai 7, D-60590 Frankfurt am Main, Germany.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural