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Title: Correlation between polimorfizm of GTP cyclohydrolase 1 and endothelial dysfunction in patients with type 2 diabetes

Abstract:

The bioavailability of tetrahydrobiopterin (BH4) is critical in the regulation of vascular function, as it controls the balance between the production of nitric oxide and superoxide by the endothelial nitric oxide synthase. Recent evidence suggests that genetic variation of GTP cyclohydrolase I, a rate limiting enzyme in BH4 production may be important in regulating vascular function. While some papers point to a “pain protective haplotype“ (rs10483639, rs3783641, rs8007267) as critical for vascular function, others indicate the rs841 3’UTR polymorphism is important. . Polymorphisms created two haplotype blocks in polish diabetics population: rs10483639, rs841, rs3783641, and second rs10137071 rs8007267. Haplotype block 1 was associated with plasma markers of oxidative stress and endothelial integrity, with the strongest association for rs841, although all studied SNPs showed statistically significant relationships. Interestingly, flow mediated dilatation, a marker of endothelial function, was only associated with the rs841 polymorphism and not with the remainder of the haplotype block. Interestingly, in this diabetic cohort, none of the GTP-CH1 polymorphisms were associated with carotid atherosclerosis as measured by intima-media thickness. These studies identify the rs841 polymorphism of the GTP cyclohydrolase I gene as a critical determinant of both vascular function and oxidative stress while the “pain protective haplotype” is most likely a marker of this association. Studies of how the rs841 polymorphism affects GTP-CH1 mRNA and protein levels are needed to define its role in vascular disease.

Level of degree:

2 - studia doktoranckie

Degree discipline:

genetyka ; patofizjologia ; biochemia

Degree grantor:

Wydział Lekarski

Promoter:

Tomasz Guzik

Date issued:

2010

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:800

Call number:

ZB-112127

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Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego - Collegium Medicum

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Last modified:

Oct 8, 2019

In our library since:

Nov 21, 2012

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Number of object content views in PDF format

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All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/800

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ZB-112127 Oct 8, 2019
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