Izabella Dunin-Wilczyńska

Nucleotide variants of genes encoding components of the Wnt signalling pathway and the risk of non‐syndromic tooth agenesis

Tooth agenesis is one of the most common dental anomalies, with a complex and not yet fully elucidated aetiology. Given the crucial role of the Wnt signalling pathway during tooth development, the purpose of this study was to determine whether nucleotide variants of genes encoding components of this signalling pathway might be associated with hypodontia and oligodontia in the Polish population. A set of 34 single nucleotide polymorphism (SNPs) in 13 WNT and WNT‐related genes were analyzed in a group of 157 patients with tooth agenesis and a properly matched control group (n = 430). In addition, direct sequencing was performed to detect mutations in the MSX1, PAX9 and WNT10A genes. Both single‐marker and haplotype analyses showed highly significant association between SNPs in the WNT10A gene and the risk for tooth agenesis. Moreover, nine pathogenic mutations within the coding region of the WNT10A gene were identified in 26 out of 42 (62%) tested patients. One novel heterozygous mutation was identified in the PAX9 gene. Borderline association with the risk of non‐syndromic tooth agenesis was also observed for the APC, CTNNB1, DVL2 and WNT11 polymorphisms. In conclusion, nucleotide variants of genes encoding important components of the Wnt signalling pathway might influence the risk of tooth agenesis.

Association of DVL2 and AXIN2 gene polymorphisms with cleft lip with or without cleft palate in a Polish population.

BACKGROUND Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital anomalies, with a complex and still not fully understood etiology. Given the important role of the Wnt/β-catenin pathway during craniofacial development, we decided to test the hypothesis that common polymorphic variants of the genes encoding crucial components of this signaling pathway might contribute to the risk of NSCL/P in the Polish population. METHODS A set of 19 single nucleotide polymorphisms (SNPs) in the APC, AXIN1, AXIN2, CTNNB1, DVL2, and GSK-3β genes were analyzed using restriction fragment length polymorphism and high-resolution melting curve methods in a group of 280 patients with NSCL/P and a properly matched control group (n = 330). RESULTS Both single-marker and haplotype analyses showed an association between SNPs in the DVL2 gene and the risk for NSCL/P. The strongest association was found under an overdominant model for the rs35594616 variant located in the exonic sequence of DVL2 (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.37-2.62; p < 0.0001). Moreover, the gene-gene interaction analysis revealed a significant epistatic interaction between DVL2 gene SNPs in the susceptibility to orofacial clefts. Borderline association with a decreased risk of NSCL/P was also observed for the AXIN2 rs3923087 variant (dominant model OR, 0.69; 95% CI, 0.50-0.95; p = 0.03). CONCLUSION This study suggests that polymorphic variants of the Wnt/β-catenin pathway genes have a role in the susceptibility to orofacial clefts. The DVL2 and AXIN2 genes might be candidate genes for this craniofacial anomaly in the Polish population. Birth Defects Research (Part A), 2012.

Polymorphisms in CHDH gene and the risk of tooth agenesis

BACKGROUND Tooth agenesis is one of the most common anomalies of human dentition and is due to a complex and not fully elucidated etiology. The purpose of this study was to evaluate the possibility that polymorphic variants of genes encoding the main folate and choline metabolism enzymes might be associated with the risk of hypodontia in the Polish population. METHODS AND RESULTS We analyzed 21 polymorphisms of 13 candidate genes and found that single nucleotide polymorphisms (SNPs) in the CHDH gene are significantly correlated with the risk of dental agenesis. The strongest association was found for the SNP located in the intronic sequence of CHDH. Individuals carrying one copy of the rs6445606 C allele had an over two-fold decreased risk of having hypodontia (odds ratio [OR]CTvsTT=0.434; 95% confidence interval [CI], 0.2724-0.6915; p=0.0004; pcorr=0.0084). A reduced risk of tooth agenesis was also observed in individuals with one or two copies of the rs6445606 C allele compared to T allele carriers (ORCT+CCvsTT=0.524; 95% CI, 0.3386-0.8097; p=0.0035; pcorr=0.0735). Moreover, the gene-gene interaction analysis revealed a significant epistatic interaction between CHDH (rs6445606) and PLD2 (rs3764897) in the susceptibility to hypodontia (p=0.004). CONCLUSION Our study identified CHDH and PLD2 as novel candidate genes, the nucleotide variants of which could be associated with the risk of tooth agenesis.

Genetic variants in BRIP1 (BACH1) contribute to risk of nonsyndromic cleft lip with or without cleft palate.

BACKGROUND The etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) is very complex and still not well elucidated. Given the critical role of DNA damage repair in the embryonic development, we decided to test the hypothesis that polymorphisms of selected DNA repair genes might contribute to the risk of NSCL/P in the Polish population. METHODS Analysis of 36 polymorphisms in 12 DNA damage repair genes (ATM, BLM, BRCA1, BRIP1, E2F1, MLH1, MRE11A, MSH2, MSH6, NBN, RAD50, and RAD51) was conducted using TaqMan assays in a group of 263 NSCL/P patients and matched control group (n = 526). RESULTS Statistical analysis of genotyping results revealed that nucleotide variants in the BRIP1 (BACH1) gene were associated with the risk of NSCL/P. Under assumption of a dominant model, the calculated odds ratios (ORs) for BRIP1 rs8075370 and rs9897121 were 1.689 (95% confidence interval [CI], 1.249-2.282; p = 0.0006) and 1.621 (95% CI, 1.200-2.191; p = 0.0016), respectively. These results were statistically significant even after applying multiple testing correction. Additional evidence for a causative role of BRIP1 in NSCL/P etiology was provided by haplotype analysis. Borderline association with a decreased risk of this anomaly was also observed for BLM rs401549 (ORrecessive = 0.406; 95% CI, 0.223-1.739; p = 0.002) and E2F1 rs2071054 (ORdominant = 0.632; 95% CI, 0.469-0.852; p = 0.003). CONCLUSION Our study suggests that polymorphic variants of DNA damage repair genes play a role in the susceptibility to NSCL/P. BRIP1 might be novel candidate gene for this common developmental anomaly.

BMI in patients with obstructive sleep apnea

Abstract Obstructive sleep apnea (OSA) is a disease of multicasual etiology. The risk factors include obesity, among other issues. Hence, it is extremely important to determine the effect of body weight on the severity of OSA. The aim of the study was to evaluate the influence of the body weight expressed as body mass index (BMI), on the value of upper airways diameter and on the AHI (Apnea-Hypopnea Index) value. The study was comprised of 41 patients diagnosed with OSA by way of polysomnography. Each patient was first examine via a lateral cephalometric image of the skull, which served to measure the upper and lower diameter of the upper airways. BMI was also calculated for each patient. Statistical analysis was carried out in accordance with Pearson’s correlation coefficient test. Our work demonstrated a negative correlation between BMI and the diameter of the upper airways, and a positive correlation between BMI and AHI value. We thus put forward that the increase in body weight in patients with OSA can contribute to the severity of the disease, regardless of the fact that it may not lead to a reduction of the lumen of the upper airways.

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

BACKGROUND Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common structural malformation with a complex and multifactorial aetiology. Associations of abnormalities in phenylalanine metabolism and orofacial clefts have been suggested. METHODS Eight single nucleotide polymorphisms (SNPs) of genes encoding phenylalanine hydroxylase (PAH) and large neutral l-amino acid transporter type 1 (LAT1), as well as the PAH mutation that is most common in the Polish population (rs5030858; R408W), were investigated in 263 patients with NSCL/P and 270 matched controls using high resolution melting curve analysis (HRM). RESULTS We found that two polymorphic variants of PAH appear to be risk factors for NSCL/P. The odds ratio (OR) for individuals with the rs7485331 A allele (AC or AA) compared to CC homozygotes was 0.616 (95% confidence interval [CI]=0.437-0.868; p=0.005) and this association remains statistically significant after multiple testing correction. The PAH rs12425434, previously associated with schizophrenia, was borderline associated with orofacial clefts. Moreover, haplotype analysis of polymorphisms in the PAH gene revealed a 4-marker combination that was significantly associated with NSCL/P. The global p-value for a haplotype comprised of SNPs rs74385331, rs12425434, rs1722392, and the mutation rs5030858 was 0.032, but this association did not survive multiple testing correction. CONCLUSION This study suggests the involvement of the PAH gene in the aetiology of NSCL/P in the tested population. Further replication will be required in separate cohorts to confirm the consistency of the observed association.

The cooperation between orthodontists and surgeons in treating facial skeletal deformities

Abstract Face skeletal deformities have been confusing both doctors and patients for ages. The harmony of the face exerts huge influence not only on one’s psyche but also the behavior and the individual’s social and professional status. In this study we present a procedure of treating skeletal malocclusion. It was performed using various orthodontic methods, like the alteration of the growth of jaws and camouflage applied in appropriate age groups. We paid special attention to the close cooperation between the orthodontist and the surgeon, which hugely facilitates curing the most complex, multi-dimensional deformities. In this study, we present our own materials concerning the effects of cooperation between two departments of Medical University of Lublin, namely the Chair and Clinic of Maxillofacial Surgery and Department of Jaw Orthopedics.

Width of dental arches in patients with maxillary midline diastema

BACKGROUND The aims of the study were as follows: (1) to examine the width of the dental arches of patients with maxillary midline diastema and compare it with control group; (2) to investigate the impact of the width of upper dental arch on the width of diastema. MATERIALS AND METHODS Diagnostic orthodontic plaster models of 102 patients with permanent dentition were studied. Patients were divided into two groups: study group with diastema and control group without diastema. Patients with severe malocclusion, craniofacial diseases, hypodontia and microdontia and pa-tients with periodontal disease were excluded. The transpalatal width of palate, premolar and molar arch widths in Ponts points of upper and lower jaw were measured using digital calliper. The results were statistically analysed. RESULTS Analysis showed a significant correlation between presence of diastema and premolar and molar width of the dental arches for both upper and lower jaw. Studied widths were larger in patients with diastema compared to the group without diastema. Analysis of the transpalatal width showed statistically significant differences between the study group and the control group. Analysis of widths of diastema and transpalatal widths showed that there was not statistically sig-nificant correlation. CONCLUSIONS Patients with diastema had increased in size in both the premolar and molar width of the dental arches. Increase the width affect to both upper and lower dental arch. Patients with diastema also were characterised by often occurrence of normal or increased of the transpalatal width but the width of the diastema did not correlate with the width of the palate. (Folia Morphol 2018; 77, 2: 340-344).

The size of anterior teeth in patients with gaps in the upper dental arch.

BACKGROUND The aim of this study was to assess the size of upper incisors and canines in patients with gaps in the upper dental arch, especially medium gap between upper central incisors. MATERIALS AND METHODS Diagnostic orthodontic models of 30 adult patients with full permanent dentition with diastema in the upper arch were studied. Patients with severe malocclusion, missing teeth and periodontal disease were excluded. Width-to-length (W/L) ratio of the clinical crown of the central, lateral incisors and canines for both sides was measured. Together 180 teeth were tested. The results were compared with the values indicated by Sterrett et al. RESULTS In all patients, the clinical crowns of central incisors were symmetrical. In most cases, a higher W/L ratio was found, which indicates that the clinical crowns of medial incisors were too broad in relation to the length. Lateral incisors: In most cases, the ratio was the same for the right and the left side; however, a few patients had asymmetry of lateral incisors. Most of the lateral incisors had higher W/L ratios, which means that the teeth were wider than they were long; some had reduced ratios and only in one case the ratio was proper. Canines were also asymmetrical, and none of the canine exhibited perfect proportions. The vast majority showed increased W/L ratio of the clinical crown. In several cases, the W/L ratio was decreased. CONCLUSIONS Patients with gaps between the teeth have abnormal W/L ratio of the clinical crowns of the upper front teeth. The values were increased in the majority of cases, which indicates that the front teeth were wider than they were long in patients with gaps. Moreover, despite the disturbed W/L proportions, central incisors remained symmetrical. In contrast, lateral incisors and canines more often exhibited asymmetries.

Evaluation of upper airways depth among patients with skeletal Class I and III

BACKGROUND The aim of this study was to determine the value of upper and lower pharyngeal depth among patients with skeletal Class III malocclusion on lateral cephalograms, as well as to examine the relationship between SNA, SNB, and ANB angles, along with Wits appraisal and the cross-sectional value of upper airway space at the level of the soft palate and tongue base among patients with skeletal Class I and III. MATERIALS AND METHODS The material consisted of lateral cephalograms taken from 80 patients living in the Lubelskie voivodeship. The study group consisted of cephalograms of 50 patients with skeletal Class III malocclusion (17 male and 33 female), whereas the control group consisted of 30 roentgenograms of patients with Class I malocclusion with proper jaw to mandible relation (14 maleand 16 female). The study and the control group shared no statistically significant differences considering basic sociographic data such as gender (chi = 1.267, p = 0.26)and age (U = 727.5, p = 0.82). The upper and lower pharyngeal depths were assessed with the use of McNamaras method. Spearmans rho test, Mann--Whitneys U test, and chi test were used for statistical analysis. RESULTS Among both males and females the pharyngeal depths were greater considering patients with skeletal Class III in comparison to patients with Class Imalocclusion (p < 0.001). Furthermore, it was determined that the lower as well as the upper pharyngeal width is statistically significantly dependent on ANB and SNB angles and Wits appraisal (p < 0.001). CONCLUSIONS Pharyngeal width at the level of the soft palate and tongue base depends on skeletal class, namely ANB angle and Wits appraisal; it increases with the increase of SNB angle (forward movement of the mandible). The SNA angle (position of the maxilla) does not influence the anterior-posterior nasopharyngeal dimension.