Hozyasz Kamil K, Mostowska Adrianna, Wójcicki Piotr, Lasota Agnieszka, Zadurska Małgorzata, Dunin-Wilczyńska Izabela, Jagodziński Paweł P
Department of Paediatrics, Institute of Mother and Child, 17a Kasprzaka Str., 01-211, Warsaw, Poland.
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
Mol Neurobiol. 2016 Jan;53(1):769-776. doi: 10.1007/s12035-015-9342-8. Epub 2015 Jul 28.
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.
由GCH1基因编码的GTP环化水解酶缺乏会导致两种神经疾病：HPABH4B型高苯丙氨酸血症和多巴反应性肌张力障碍。参与神经递质代谢和运动系统的基因可能影响腭的形成。本研究的目的是分析GCH1基因的多态性变异作为非综合征性唇裂伴或不伴腭裂（NSCL/P）的危险因素。对281例NSCL/P患者和574例对照进行了9种多态性的基因分型。GCH1变异体rs17128077与NSCL/P风险高1.7倍相关（95%CI = 1.224 - 2.325；p = 0.001）。我们还发现rs8004018和rs17128050变异体与口腔裂隙风险增加之间存在显著相关性（p趋势分别为0.003和0.004）。rs17128050和rs8004018的全球单倍型关联证据最为显著（p校正 = 0.0152）。本研究表明，NSCL/P的风险与GCH1基因中与四氢生物蝶呤（BH4）代谢相关的变异有关，并为中枢神经系统形态学/功能变化与口面部裂隙之间的关系提供了一些证据。
