کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2149732 1089879 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clinical genetics of functionally mild non-coding GTP cyclohydrolase 1 (GCH1) polymorphisms modulating pain and cardiovascular risk
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Clinical genetics of functionally mild non-coding GTP cyclohydrolase 1 (GCH1) polymorphisms modulating pain and cardiovascular risk
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Reviews in Mutation Research - Volume 659, Issue 3, September–October 2008, Pages 195–201
نویسندگان
, , , , ,