Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population

Mostowska, Adrianna; Hozyasz, Kamil K.; Wójcicki, Piotr; Biedziak, Barbara; Paradowska, Patrycja; Jagodzińśki, Paweł P.

doi:10.1002/bdra.20687

Cited by 65 publications

(54 citation statements)

References 45 publications

(61 reference statements)

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“…Positive association between the IRF6 rs642961 variant and nsCL/P has been confirmed by multiple studies involving various ethnicities [21][22][23][24] . Also, our results are in accordance with the findings from two case-control studies on Central European populations which showed similar magnitudes of odds ratios 10,19 . Nonetheless, one European and two non-European studies did not identify any association between this variant and nsCL/P (ref.…”

Section: Discussionsupporting

confidence: 92%

“…The allelic frequencies for all the tested SNPs in control group (Table 1) did not differ significantly from an- other publicly available data on Caucasian populations (http://www.ensembl.org) and were also similar to the frequencies reported from other case-control studies conducted on Central European populations 10,12,19,20 . With respect to allele distributions, the significant associations with nsCL/P risk, persisting even after Bonferroni correction for multiple comparisons, were found for SNPs at the 1q32, 8q24 and 17q22 loci.…”

Section: Resultssupporting

confidence: 81%

“…The rs987525 showed nominal significance in all of the models of inheritance tested, with a 1.5 to more than twofold increase in risk. Similar results for rs987525 were obtained in a study on the Central European sample which showed a 1.7-fold increase in the risk of nsCL/P under the dominant inheritance model 19 . Although the association between rs987525 and the risk of nsCL/P has been replicated in numerous studies on various ethnicities [28][29][30][31] , the underlying functional mechanism remains unknown as rs987525 resides in a region of the genome containing no known genes 12 .…”

Section: Discussionsupporting

confidence: 85%

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Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Salagovic¹,

Klimčáková²,

Zabavnikova³

et al. 2017

BIOMED PAP

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Background. Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is the most common orofacial birth defect with an aetiology involving both genetic and environmental factors. Genome-wide association studies (GWAS) have identified several genomic susceptibility regions for nsCL/P. In the present study, the three well established single nucleotide polymorphisms (SNPs) identified by GWAS (rs987525 at 8q24, rs7078160 at 10q25, and rs227731 at 17q22 loci) and one SNP identified by candidate gene study (rs642961 in IRF6 gene at 1q32 locus) were analysed for an association with nsCL/P in Slovak population. Methods. Nucleotide variants were genotyped in 165 nsCL/P patients and 326 unaffected controls. All variants of interest were genotyped using high-resolution melting analysis after real-time PCR. Results. We found significant differences between patient and control groups with respect to the allele and genotype frequencies for the SNPs at the 1q32, 8q24, and 17q22 loci. SNP at the 10q25 locus showed a trend toward association with nsCL/P risk. Conclusions.The results suggest that SNPs at the 1q32, 8q24 and 17q22 loci may contribute to the nsCL/P risk in Slovak population.

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Section: Discussionsupporting

confidence: 92%

Section: Resultssupporting

confidence: 81%

Section: Discussionsupporting

confidence: 85%

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Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Salagovic¹,

Klimčáková²,

Zabavnikova³

et al. 2017

BIOMED PAP

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“…Only one in vivo study, conducted in a small sample, suggested that rs642961 genotypes modulate IRF6 expression in an allele-dosage manner in skin lip from affected patients [Pan et al, 2010]. The SNP rs590223 (A>G) also is predicted to modulate in vivo the transcriptional levels of IRF6 in liver cells [Schadt et al, 2008], and its association with NSCL/P is controversial [Jagom€ agi et al, 2010;Mostowska et al, 2010].…”

Section: Introductionmentioning

confidence: 95%

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population

Brito

Bassi

Masotti

et al. 2012

American J of Med Genetics Pt A

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Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a complex disorder with a worldwide incidence estimated at 1:700. Among the putative susceptibility loci, the IRF6 gene and a region at 8q24.21 have been corroborated in different populations. To test the role of IRF6 in NSCL/P predisposition in the Brazilian population, we conducted a structured association study with the SNPs rs642961 and rs590223, respectively, located at 5' and 3' of the IRF6 gene and not in strong linkage disequilibrium (LD), in patients from five different Brazilian locations. We also evaluated the effect of these SNPs in IRF6 expression in mesenchymal stem cells (MSC). We observed association between rs642961 and cleft lip only (CLO) (P=0.009; odds ratio (OR) for AA genotype=1.83 [95% Confidence interval (CI), 0.64-5.31]; OR for AG genotype=1.72 [95% CI, 1.03-2.84]). This association seems to be driven by the affected patients from Barbalha, a location which presents the highest heritability estimate (H2=0.85), and the A allele at rs642961 is acting through a dominant model. No association was detected for the SNP rs590223. We did not find any correlation between expression levels and genotypes of the two loci, and it is possible that these SNPs have a functional role in some specific period of embryogenesis.

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“…In humans, research suggests that various growth factors (e.g. TGFA, FGF10, FGFR1), receptors, and transcription factors are important in CL/P development (Mostowska et al, 2010). The CL/P-affected children have to undergo several invasive medical procedures, and therefore it is a imperative for a better understanding of abnormal palatogenesis and identification of modifiable risk factors.…”

Section: Introductionmentioning

confidence: 99%

Malonylcarnitine in Newborns with Non‐syndromic Cleft Lip with or without Cleft Palate

Hozyasz

Oltarzewski²,

Dudkiewicz

2010

Int J Oral Sci

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Aim Malonyl-CoA is regarded as a key signaling molecule in mammalian cells. It is converted to acetyl-CoA, and to a lesser extent, to malonyl acid and malonylcarnitine (C3DC).Availability of carnitine has been reported to be essential for the developing fetus. The objectives of the present study were to analyze associations of malonylcarnitine, acetylcarnitine (C2), and free carnitine (C0) in subjects with orofacial clefts. MethodologyWe performed a retrospective analysis of carnitine concentration obtained from a newborn screening program carried out in our institution. Concentrations of whole blood malonylcarnitine, acetylcarnitine, and free carnitine were measured using tandem mass spectrometry.The study group consisted of 51 children with nonsyndromic cleft lip with or without cleft palate. In total, 106 healthy children without congenital anomalies served as controls. Cut-off points were established using likelihood ratio values. ResultsThe mean concentration of malonylcarnitine in the cleft group was lower than that of the control group, 0.048 μmol⋅L -1 vs. 0.058 μmol⋅L -1 , respectively (P=0.009).In patients with orofacial cleft, low malonylcarnitine levels (≤0.047 μmol⋅L ConclusionThe study provides initial data indicating a potential association between decreased malonylcarnitine and abnormal palatogenesis.

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Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population

Abstract: Our findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample.

Cited by 65 publications

References 45 publications

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population

Malonylcarnitine in Newborns with Non‐syndromic Cleft Lip with or without Cleft Palate

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