Candidate genes for obstructive sleep apnea in non-syndromic children with craniofacial dysmorphisms – a narrative review

Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) – craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia – have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population

Glutathione S-transferase M1, T1, and P1 polymorphisms and periodontitis in a Caucasian population: a case-control study

Abstract Background Glutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population. Methods We analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr). Results The GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively). Conclusions This study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed

Clinical Study Haplotype Analysis of Interleukin-8 Gene Polymorphisms in Chronic and Aggressive Periodontitis

Objectives. Periodontitis is an inflammatory disease characterized by connective tissue loss and alveolar bone destruction. Interleukin-8 (IL8) is important in the regulation of the immune response. The aim of this study was to analyze four polymorphisms in the IL8 gene in relation to chronic (CP) and aggressive (AgP) periodontitis. Methods. A total of 492 unrelated subjects were included in this case-control association study. Genomic DNA of 278 patients with CP, 58 patients with AgP, and 156 controls were genotyped, using the 5 nuclease TaqMan assay, for IL8 (rs4073, rs2227307, rs2227306, and rs2227532) gene polymorphisms. Subgingival bacterial colonization was investigated by the DNA-microarray detection kit in a subgroup of subjects ( = 247). Results. Allele and genotype frequencies of all investigated IL8 polymorphisms were not significantly different between the subjects with CP and/or AgP and controls ( > 0.05). Nevertheless, the A(−251)/T(+396)/T(+781) and T(−251)/G(+396)/C(+781) haplotypes were significantly less frequent in patients with CP (2.0% versus 5.1%, < 0.02, OR = 0.34, 95% CI: 0.15-0.78, resp., 2.0% versus 4.5%, < 0.05, OR = 0.41, 95% CI: 0.18-0.97) than in controls. Conclusions. Although none of the investigated SNPs in the IL8 gene was individually associated with periodontitis, some haplotypes can be protective against CP in the Czech population

Emotional stimuli candidates for behavioural intervention in the prevention of early childhood caries: a pilot study

Abstract Background Oral diseases, such as early childhood caries (ECC), have a complex etiology with common, behaviour-related risk factors. Appropriately targeted behavioural intervention using effective tools can help to eliminate risk behaviour leading to ECC. The aim of this study was to ascertain which visual stimuli with a supporting text evoke the strongest emotional response in infants’ mothers and, therefore, are suitable candidates for inclusion in behavioural interventions within the prevention of ECC. Methods Thirty-nine mothers of one-year-old children who filled out an originally designed electronic questionnaire, containing 20 visual stimuli with accompanying texts related to dental caries (10/10 with positive/negative intended emotional response), were included in this cross-sectional study. The emotional impact of each stimulus in the mothers was evaluated using the Self-Assessment Manikin (SAM) technique, which represents three emotional dimensions: valence, arousal, and dominance. Results Each of the stimuli was assessed by the mothers of infants based on its emotional impact. The real emotional response (evaluated according to the median of valence) was in line with the primarily intended response in 90% of cases (p < 0.05). The text with a warning evoked a greater emotional response (evaluated according to the median of arousal) in mothers than only the informative instruction (p < 0.05). The relationship between arousal and valence (r = − 0.99; p < 0.05) indicates that the more aversive stimuli raise higher arousal. The significant correlation between valence and dominance shows that the more positive the stimuli, the higher feeling of control over the evoked emotion the mothers have (r = 0.83; p < 0.05), and, on the contrary, the lowest control over emotion is correlated with higher arousal (r = − 0.85; p < 0.05). Generally, mothers rated themselves as in high control of their emotions over the individual stimuli. Conclusions This pilot study proved that negative pictorial and text warnings about the risks of developing caries had the potential to evoke strong emotional responses in the mothers of infants. We identified three visual stimuli that could be included in future extensive motivation material in an attempt to affect the preventive behaviour of mothers, and thus the oral health of their infants

A SNaPshot Assay for Determination of the Mannose-Binding Lectin Gene Variants and an Algorithm for Calculation of Haplogenotype Combinations

Mannose-binding lectin (MBL) deficiency caused by the variability in the MBL2 gene is responsible for the susceptibility to and severity of various infectious and autoimmune diseases. A combination of six single nucleotide polymorphisms (SNPs) has a major impact on MBL levels in circulation. The aim of this study is to design and validate a sensitive and economical method for determining MBL2 haplogenotypes. The SNaPshot assay is designed and optimized to genotype six SNPs (rs1800451, rs1800450, rs5030737, rs7095891, rs7096206, rs11003125) and is validated by comparing results with Sanger sequencing. Additionally, an algorithm for online calculation of haplogenotype combinations from the determined genotypes is developed. Three hundred and twenty-eight DNA samples from healthy individuals from the Czech population are genotyped. Minor allele frequencies (MAFs) in the Czech population are in accordance with those present in the European population. The SNaPshot assay for MBL2 genotyping is a high-throughput, cost-effective technique that can be used in further genetic-association studies or in clinical practice. Moreover, a freely available online application for the calculation of haplogenotypes from SNPs is developed within the scope of this project