Association of common variants in PAH and LAT1 with non-syndromic cleft lip with or without cleft palate (NSCL/P) in the Polish population

Hozyasz, Kamil K.; Mostowska, Adrianna; Wójcicki, Piotr; Lasota, Agnieszka; Wołkowicz, Anna; Dunin-Wilczyńska, Izabella; Jagodzińśki, Paweł P.

doi:10.1016/j.archoralbio.2014.01.003

Cited by 2 publications

(4 citation statements)

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“…The PAH rs7485331 and rs12425434 were reported to influence susceptibility to isolated orofacial clefts (17). Mutations in the PAH gene cause phenylketonuria, the most common inborn error of amino acids metabolism in Middle East Asians and Europeans.…”

Section: Discussionmentioning

confidence: 99%

“…Five SNPs in GCH1 and PAH, previously detected to be in association with orofacial clefts risk in the Polish population (9,17), as well as rs2191349 of the AGMO-DGKB loci were evaluated in this study (Table 1). The genotyping was carried out by high-resolution melting curve analysis (HRM) on the Light Cycler 480 system (Table 2).…”

Section: Single Nucleotide Polymorphism (Snp) Selection and Genotypingmentioning

confidence: 99%

“…Polymorphic variants of GCH1 are associated with the pathogenesis of spina bifida (16) and orofacial clefts (9). The involvement of the PAHgen in the etiology of orofacial clefts was reported in the Polish population (17). AGMO belongs to candidate genes for congenital heart anomalies in humans (18).…”

Section: Introductionmentioning

confidence: 99%

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Polymorphic Variants of BH4 Pathway Genes and Isolated Hypospadias Risk

Hozyasz

Mostowska²,

Kowal

et al. 2020

Iran J Pediatr

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Background: Hypospadias (HS) is one of the most common congenital malformations. Complications of corrective surgery in HS correlate with patients’ opinions on their voiding ability and sexual life as adults. Etiology of HS involves both genetic and environmental factors. GCH1, which belongs to recently identified urothelial genes influencing voiding behavior, encodes rate-limiting enzyme catalyzing the production of tetrahydrobiopterin (BH4). A requirement for BH4, a metabolite structurally related to folic acid and riboflavin, in embryonic development was reported. Objectives: The aim of the present study was to investigate the association of selected polymorphic variants of BH4 pathway genes with hypospadias. Methods: We performed an analysis of 6 SNPs of GCH1, PAH and AGMO-DGKB loci in a group of 166 boys with isolated hypospadias and a properly matched control group. Results: There was no evidence for either allelic or genotypic association with the risk of HS for the tested nucleotide variants (rs12425434, rs7485331, rs17128050, rs8004018, rs17128077, rs2191349). The lack of association with single SNPs was confirmed at the haplotype level. The exhaustive multifactor dimensionality reduction (MDR) analysis revealed no significant interactive effect of polymorphic variants of BH4 pathway genes on HS susceptibility. Conclusions: The presented results did not support an association between SNPs of GCH1 and PAH and the risk of HS.

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Section: Discussionmentioning

confidence: 99%

Section: Single Nucleotide Polymorphism (Snp) Selection and Genotypingmentioning

confidence: 99%

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Polymorphic Variants of BH4 Pathway Genes and Isolated Hypospadias Risk

Hozyasz

Mostowska²,

Kowal

et al. 2020

Iran J Pediatr

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“…BH4 is an essential cofactor for three aromatic amino acid hydroxylases, including tyrosine hydroxylase (rate-limiting enzyme in dopamine biosynthesis), tryptophan hydroxylase (TPH2), and phenylalanine hydroxylase (PAH), as well as three isoforms of nitric oxide synthase (NOS), which catalyses the synthesis of nitric oxide from arginine, and alkylglycerol monooxygenase. Interestingly, in our previous studies, we showed that polymorphic variants of PAH and TPH2 as well as haplotype combinations of the TPH2 SNPs were significantly correlated with NSCL/P in the Polish population [ 27 , 28 ]. Several studies have observed orofacial clefting and midfacial hypoplasia in offspring of women with untreated hyperphenylalaninemia [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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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Association of common variants in PAH and LAT1 with non-syndromic cleft lip with or without cleft palate (NSCL/P) in the Polish population

Cited by 2 publications

References 39 publications

Polymorphic Variants of BH4 Pathway Genes and Isolated Hypospadias Risk

Polymorphic Variants of BH4 Pathway Genes and Isolated Hypospadias Risk

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

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