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Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts

A deficiency of GTP cyclohydrolase, encoded by the GCH1 gene, results in two neurological diseases: hyperphenylalaninaemia type HPABH4B and DOPA-responsive dystonia. Genes involved in neurotransmitter metabolism and motor systems may contribute to palatogenesis. The purpose of the study was to analy...

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Autores principales: Hozyasz, Kamil K., Mostowska, Adrianna, Wójcicki, Piotr, Lasota, Agnieszka, Zadurska, Małgorzata, Dunin-Wilczyńska, Izabela, Jagodziński, Paweł P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703629/
https://www.ncbi.nlm.nih.gov/pubmed/26215833
http://dx.doi.org/10.1007/s12035-015-9342-8
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author Hozyasz, Kamil K.
Mostowska, Adrianna
Wójcicki, Piotr
Lasota, Agnieszka
Zadurska, Małgorzata
Dunin-Wilczyńska, Izabela
Jagodziński, Paweł P.
author_facet Hozyasz, Kamil K.
Mostowska, Adrianna
Wójcicki, Piotr
Lasota, Agnieszka
Zadurska, Małgorzata
Dunin-Wilczyńska, Izabela
Jagodziński, Paweł P.
author_sort Hozyasz, Kamil K.
collection PubMed
description A deficiency of GTP cyclohydrolase, encoded by the GCH1 gene, results in two neurological diseases: hyperphenylalaninaemia type HPABH4B and DOPA-responsive dystonia. Genes involved in neurotransmitter metabolism and motor systems may contribute to palatogenesis. The purpose of the study was to analyse polymorphic variants of the GCH1 gene as risk factors for non-syndromic cleft lip with or without cleft palate (NSCL/P). Genotyping of nine polymorphisms was conducted in a group of 281 NSCL/P patients and 574 controls. The GCH1 variant rs17128077 was associated with a 1.7-fold higher risk for NSCL/P (95 %CI = 1.224–2.325; p = 0.001). We also found a significant correlation between the rs8004018 and rs17128050 variants and an increased risk of oral clefts (p (trend) = 0.003 and 0.004, respectively). The best evidence of the global haplotype association was observed for rs17128050 and rs8004018 (p (corr) = 0.0152). This study demonstrates that the risk of NSCL/P is associated with variants of the GCH1 gene related to BH4 metabolism and provides some evidence of the relationships between morphological/functional shifts in the central nervous system and orofacial clefts.
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spelling pubmed-47036292016-01-12 Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts Hozyasz, Kamil K. Mostowska, Adrianna Wójcicki, Piotr Lasota, Agnieszka Zadurska, Małgorzata Dunin-Wilczyńska, Izabela Jagodziński, Paweł P. Mol Neurobiol Article A deficiency of GTP cyclohydrolase, encoded by the GCH1 gene, results in two neurological diseases: hyperphenylalaninaemia type HPABH4B and DOPA-responsive dystonia. Genes involved in neurotransmitter metabolism and motor systems may contribute to palatogenesis. The purpose of the study was to analyse polymorphic variants of the GCH1 gene as risk factors for non-syndromic cleft lip with or without cleft palate (NSCL/P). Genotyping of nine polymorphisms was conducted in a group of 281 NSCL/P patients and 574 controls. The GCH1 variant rs17128077 was associated with a 1.7-fold higher risk for NSCL/P (95 %CI = 1.224–2.325; p = 0.001). We also found a significant correlation between the rs8004018 and rs17128050 variants and an increased risk of oral clefts (p (trend) = 0.003 and 0.004, respectively). The best evidence of the global haplotype association was observed for rs17128050 and rs8004018 (p (corr) = 0.0152). This study demonstrates that the risk of NSCL/P is associated with variants of the GCH1 gene related to BH4 metabolism and provides some evidence of the relationships between morphological/functional shifts in the central nervous system and orofacial clefts. Springer US 2015-07-28 2016 /pmc/articles/PMC4703629/ /pubmed/26215833 http://dx.doi.org/10.1007/s12035-015-9342-8 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Hozyasz, Kamil K.
Mostowska, Adrianna
Wójcicki, Piotr
Lasota, Agnieszka
Zadurska, Małgorzata
Dunin-Wilczyńska, Izabela
Jagodziński, Paweł P.
Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts
title Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts
title_full Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts
title_fullStr Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts
title_full_unstemmed Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts
title_short Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of Orofacial Clefts
title_sort nucleotide variants of the bh4 biosynthesis pathway gene gch1 and the risk of orofacial clefts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703629/
https://www.ncbi.nlm.nih.gov/pubmed/26215833
http://dx.doi.org/10.1007/s12035-015-9342-8
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