Contribution to Knowledge on Bioapatites: Does Mg Level Reflect the Organic Matter and Water Contents of Enamel?

The matter constituting the enamels of four types of organisms was studied. The variability of the ions was presented in molar units. It was proven that the changes in water contents of the enamel are significantly positively related to changes in Mg; inversely, there is also a strong connection with changes in Ca and P, the main components of bioapatite. The variability in the organic matter has the same strong and positive characteristics and is also coupled with changes in Mg contents. Amelogenins in organic matter, which synthesize enamel rods, likely have a role in adjusting the amount of Mg, thus establishing the amount of organic matter and water in the whole enamel; this adjustment occurs through an unknown mechanism. Ca, P, Mg, and Cl ions, as well as organic matter and water, participate in the main circulation cycle of bioapatites. The selection of variations in the composition of bioapatite occurs only along particular trajectories, where the energy of transformation linearly depends on the following factors: changes in the crystallographic d parameter; the increase in the volume, V, of the crystallographic cell; the momentum transfer, which is indirectly expressed by ΔsinΘ value. To our knowledge, these findings are novel in the literature. The obtained results indicate the different chemical and crystallographic affinities of the enamels of selected animals to the human ones. This is essential when animal bioapatites are transformed into dentistic or medical substitutes for the hard tissues. Moreover, the role of Mg is shown to control the amount of water in the apatite and in detecting organic matter in the enamels.

Crisis Experience and Purpose in Life in Men and Women: The Mediating Effect of Gratitude and Fear of COVID-19.

AIM: This study investigated whether gratitude and fear of COVID-19 mediated the relationship between crisis experience during the pandemic and purpose in life in men and women. METHODS: Six hundred and five participants aged between 18 and 60 years (M = 25.6; SD = 8.39) completed the Gratitude, Resentment, and Appreciation Scale-Short Form (GRAT-S), Fear of COVID-19 Scale, and Purpose in Life Test (PIL). In addition, the respondents were questioned about life crises during the previous six months (e.g., the death of a loved one or illness). RESULTS: Men and women differed in their endorsement of gratitude or fear of COVID-19 as a mediator. Women's experiences of the crisis related both directly and indirectly to purpose in life, with gratitude and fear of COVID-19 mediating this relationship. In men, only the indirect path, from crisis experience, through gratitude, to purpose in life, turned out to be significant. CONCLUSION: The results of this study suggest that coping styles differ in men and women and, as a consequence, that crisis interventions need to take gender into account.

Quantitative Description of Isomorphism in the Series of Simple Compounds.

The introduction of the notion of energy change resulting from the ion exchange in apatites leads to the question: how can some simple isomorphic series be described using the mentioned idea? We concentrated on the simple isomorphic series of compounds: apatite, bioapatite, calcite, aragonite, celestine, K-, Zn- and Cu-Tutton's salts. It was demonstrated in all the series, except Tutton's salts, that the change in energy and the change in the crystal cell volume are, in a simple way, dependent on the change in the ionic radii of the introduced ions. The linear relationships between the variations in energy and in the universal crystallographic dimension d were derived from the earlier equations and proven based on available data. In many cases, except the Tutton's salts, linear dependence was discovered between the change in energy and the sinus of universal angle Θ, corresponding to the change in momentum transfer. In the same cases, linear dependencies were observed between the energy changes and the changes in the volumes of crystallographic cells, and mutually between changes in the crystallographic cell volume V, crystallographic dimension d, and diffraction angle Θ.

Studies on Chemical Composition, Structure and Potential Applications of Keratoisis Corals.

The chemical composition and structure of bamboo octocoral Keratoisis spp. skeletons were investigated by using: Scanning Electron Microscopy SEM, Raman Microscopy, X-ray Diffraction XRD, Laser Ablation-Inductively Coupled Plasma LA-ICP, and amino acid analyzers. Elements discovered in the nodes (mainly organic parts of the skeleton) of bamboo corals showed a very interesting arrangement in the growth ring areas, most probably enabling the application of bamboo corals as palaeochronometers and palaeothermometers. LA-ICP results showed that these gorgonian corals had an unusually large content of bromine, larger than any other organism yet studied. The local concentration of bromine in the organic part of the growth rings of one of the studied corals grew up to 29,000 ppm of bromine. That is over 440 times more than is contained in marine water and 35 times more than Murex contains, the species which was used to make Tyrian purple in ancient times. The organic matter of corals is called gorgonin, the specific substance that both from the XRD and Raman studies seem to be very similar to the reptile and bird keratins and less similar to the mammalian keratins. The missing cross-linking by S-S bridges, absence of aromatic rings, and significant participation of ß-turn organization of peptides differs gorgonin from keratins. Perhaps, the gorgonin belongs to the affined but still different substances concerning reptile and bird keratin and in relation to the more advanced version-the mammalian one. Chemical components of bamboo corals seem to have great medical potential, with the internodes as material substituting the hard tissues and the nodes as the components of medicines.

Lip morphometry and morphologic pattern variation by ethnicity.

The aim of this research is to document and classify common lip print patterns and lip measurements, to evaluate their variations in Polish, Russian, Lithuanian women populations. 371 women (151 Lithuanians, 145 Poles, 75 Russians) from Vilnius University participated in this research. A questionnaire and lip print collection were administered. Each lip print was divided into six sextants, examined and classified. 120 women were photographed by Vectra M3 3D (Canfield Imaging Systems, USA) camera, lip morphometry was analyzed. In all lip print sextants, Type I was the most common among Lithuanians, Type III - among Polish and Type V - among Russian women. A statistically significant difference was found between Type I lip print pattern and Lithuanian ethnicity (p = 0.001) and Type III and Polish ethnicity (p = 0.015). The values of medial vertical height of cutaneous upper lip (p = 0.045), height of upper lip (p = 0.034), philtrum width (p = 0.020), height of lower vermilion (p = 0.015), upper lip vermilion area (p = 0.022), upper lip volume (p = 0.034) and total lip volume (p = 0.05) statistically significantly varied between the ethnicities. Morphometric findings were similar to other morphometric research on Caucasians.

Measurements of Energetic States Resulting from Ion Exchanges in the Isomorphic Crystals of Apatites and Bioapatites.

Developments in the field of nanostructures open new ways for designing and manufacturing innovative materials. Here, we focused on new original ways of calculating energy changes during the substitution of foreign ions into the structure of apatites and bioapatites. Using these tools, the energetic costs of ion exchanges were calculated for the exemplary cases known from the literature. It was established that the most costly were ion exchanges of some cations inside apatites and of anions, and the least costly exchanges in tetrad channel positions. Real energy expenses for bioapatites are much smaller in comparison to mineral apatites due to the limited involvement of magnesium and carbonates in the structure of hard tissues. They are of the order of several electron volts per ion. The rigorous dependences of the energy changes and crystallographic cell volumes on the ionic radii of introduced cations were proved. The differentiation of the positioning of foreign ions in locations of Ca(I) and Ca(II) could be calculated in the case of a Ca-Pb reaction in hydroxyapatite. The energetic effects of tooth aging were indicated. The ability of energy change calculation during the ion exchange for isomorphic substances widens the advantages resulting from X-ray diffraction measurements.

Hierarchy of Bioapatites.

Apatites are one of the most intensively studied materials for possible biomedical applications. New perspectives of possible application of apatites correspond with the development of nanomaterials and nanocompounds. Here, an effort to systematize different kinds of human bioapatites forming bones, dentin, and enamel was undertaken. The precursors of bioapatites and hydroxyapatite were also considered. The rigorous consideration of compositions and stoichiometry of bioapatites allowed us to establish an order in their mutual sequence. The chemical reactions describing potential transformations of biomaterials from octacalcium phosphate into hydroxyapatite via all intermediate stages were postulated. Regardless of whether the reactions occur in reality, all apatite biomaterials behave as if they participate in them. To conserve the charge, additional free charges were introduced, with an assumed meaning to be joined with the defects. The distribution of defects was coupled with the values of crystallographic parameters "a" and "c". The energetic balances of bioapatite transformations were calculated. The apatite biomaterials are surprisingly regular structures with non-integer stoichiometric coefficients. The results presented here will be helpful for the further design and development of nanomaterials.

The Prevalence and Morphology of Supernumerary Teeth in Children With Nonsyndromic Cleft Lip and Palate.

INTRODUCTION: Cleft lip with or without cleft palate (CL/P) is congenital deformity associated with hyperdontia. OBJECTIVE: To determine the prevalence and characteristics of supernumerary teeth in patients with CL/P. DESIGN: Retrospective descriptive and correlation clinical study. PATIENTS: One hundred thirteen children with cleft (age ranged 9.3-19.2; 67 males and 46 females) treated in Clinic of Congenital Facial Deformities Medical University of Lublin were included in the study. METHODS: Records evaluation was conducted regarding age, gender, cleft type (Q36, Q37-International Classification of Diseases 10th revision), cleft side, and incidence of supernumeraries. In all supernumerary teeth, size, shape, and developmental degree were analyzed and correlation between the incidence of hyperdontia with different variables was checked. Correlations were detected using chi-square and the Yates correction. RESULTS: The majority of the examined group were males-59.29% with Q37 (67.26%) and the cleft on the left side (62.83%). Hyperdontia was noted in 26.55%. Only upper lateral incisors were affected. They usually had atypical shape (56.67%), reduced size (83.33%), and delayed development (56.67%). CONCLUSIONS: The prevalence of supernumerary permanent teeth in patients with cleft was higher than in the general population. Anomaly was more frequent in male patients and occurred mainly on the cleft side. The severity of the cleft did not influenced the frequency of supernumerary teeth, their shape, size, and developmental degree. Supernumerary teeth were characterized by reduced crown size, abnormal structure, incorrect inclination, and delayed development phase.

Changes in Distribution of Dental Biofilm after Insertion of Fixed Orthodontic Appliances.

Good oral hygiene is an important factor in oral and general health, especially in orthodontic patients, because fixed appliances might impede effective oral hygiene and thus increase the risks of tooth decay, periodontal disease and general health complications. This study investigated the impact of fixed orthodontic appliances on the distribution of dental biofilm in teenagers. Supragingival plaque was assessed at T0, T1 and T2. The distribution of the biofilm was analyzed. Approximal Plaque Index (API) and Bonded Bracket Index (BBI) were used to measure the presence of dental plaque. After insertion of the fixed appliance, the dental plaque indices values in the orthodontically treated group were significantly higher (p < 0.05) than in the control group. Fixed orthodontic appliances caused significant changes in the distribution of the biofilm. This was characterized by the change of location of the dental plaque. In the orthodontic group, we observed an increase in the amount of the supragingival plaque on the vestibular surface of the teeth.

Positive Psychology in Times of Pandemic-Time Perspective as a Moderator of the Relationship between Resilience and Meaning in Life.

Resilience and meaning in life are significant indicators of psychological well-being and health, which are particularly important in the context of the COVID-19 pandemic. Therefore, they have been explored by a growing number of scientists. There has been a research gap, however, that fails to show that time perspectives also have a significant impact on the perception and building of different life aspects. The current study investigated the associations between resilience, time perspectives and meaning in life and examined the moderating role of time perspective in the relationship between resilience and meaning in life. METHODS: Participants of this cross-sectional study were 363 adults aged 18-70. Resilience Measurement Scale (SPP-25), the Zimbardo Time Perspective Inventory (ZTPI), and the Purpose in Life Questionnaire (PIL) were used. RESULTS: The findings confirmed a positive relationship between resilience, meaning in life, and positive time perspectives (Present Hedonistic and Future) and a negative link with Past Negative and Present Fatalistic perspectives. The linear regression analyses showed that Past Negative and Past Positive perspectives significantly moderated the relationship between resilience and meaning in life. The moderating effect was also confirmed in the case of past time perspectives only. CONCLUSIONS: The findings indicate the relevance of positive resources, such as resilience and positive perception of the past, in keeping the meaning in life. Understanding the effect of psychological strengths in the context of the pandemic time can be a key to providing intervention and therapeutic services fostering mental health and well-being.

Frequency of Additional Congenital Dental Anomalies in Children with Cleft Lip, Alveolar and Palate.

The aim of the study was to assess the risk of incidence of additional congenital dental anomalies in children with nonsyndromic cleft lip, alveolar and/without palate (CL/P). Hypodontia, hyperdontia and canines impaction was recognized. From patients with CL/P treated at the Clinic of Congenital Facial Deformities in Chair and Department of Jaw Orthopedics Medical University of Lublin, 56 subjects were randomly selected. On the panoramic radiographs taken at the age of 8-12 years, the angle of upper unerupted canines was measured using Westerlund's recommendations. The supernumerary teeth and hypodontia were checked. The procedures: maxillary expansion, secondary alveolar bone graft (SABG) and extraction of primary canines were noted. The frequency of canines impaction was 5.36%. Hypodontia was found in 37.5% of patients; hyperdontia was present in 23.21% of patients. No influence of procedures (expansion of the maxilla, SABG, deciduous canines extraction) on permanent maxillary canine eruption was proved. Patients with CL/P are exposed to the unfavorable position of unerupted maxillary canines most frequently in the cleft area of complete cleft. Maxillary lateral incisor on the cleft side is most frequently affected with congenital anomaly. Hypodontia and hyperdontia do not influence maxillary canine impaction. Good clinical result was achieved with an applied approach, which should be widely introduced.

Empathy, Gratitude, and Resilience - Does Gender Make a Difference? / Empatía, resiliencia y gratitud: ¿hay diferencias de género?

Past research shows most women report higher levels of empathy and gratitude than men. Although studies show relations among resilience, gratitude, and empathy, little is known on the influence of gender on the links among. The present study examined the individual difference and relations among young adults' levels of empathy, gratitude, and resilience, particularly how gender influences such relations. Participants were 214 Polish self-identified females and males' young adults, who completed self-report measures of empathy, gratitude, and resilience. Results showed that females scored higher in empathy and gratitude than males, but males reported higher levels of resilience than females. Resilience also served as a mediator between empathy and gratitude and this differed according to self-identified gender. Implications for gendered developmental research in social cognition are discussed

Investigaciones anteriores muestran que la mayoría de las mujeres reportan niveles más altos de empatía y gratitud que los hombres. Aunque los estudios muestran relaciones entre resiliencia, gratitud y empatía, se sabe poco sobre la influencia del género en los vínculos entre ellos. El presente estudio examinó las diferencias individuales y las relaciones entre los niveles de empatía, gratitud y resiliencia de los adultos, particularmente cómo el género influye en tales relaciones. En segundo lugar, se probó el papel de mediación de la resiliencia en las asociaciones entre empatía y gratitud. Los participantes fueron 214 adultos polacos (104 mujeres) autoidentificados, con edades entre 18 y 55 años (M = 28.29 años, DT = 11.19), que completaron medidas de empatía de autoinforme en línea (escala QCAE), gratitud (escala GRAT) y resiliencia (escala SPP-25). El estudio transversal se utilizó para obtener los datos. Los resultados muestran que las mujeres obtuvieron puntuaciones más altas en empatía y gratitud que los hombres, pero los hombres informaron niveles más altos de resistencia que las mujeres. La apertura a nuevas experiencias de vida (dimensión de resiliencia) surgió como el predictor más fuerte de gratitud en ambos grupos. La resiliencia también sirvió como mediador entre la empatía y la gratitud y esto difería según el género autoidentificado. Se discuten las implicaciones para la investigación del desarrollo de género en psicología positiva

PAX7 nucleotide variants and the risk of non-syndromic orofacial clefts in the Polish population.

OBJECTIVE: The etiology of non-syndromic cleft lip with or without cleft palate (nsCL/P) is multifactorial, heterogeneous, and still not completely understood. The aim of the present study was to examine the associations between common and rare PAX7 nucleotide variants and the risk of this common congenital anomaly in a Polish population. SUBJECTS AND METHODS: Eight top nsCL/P-associated PAX7 variants identified in our cleft genome-wide association study (GWAS) were selected for replication analysis in an independent group of patients and controls (n = 247 and n = 445, respectively). In addition, mutation screening of the PAX7 protein-coding region was conducted. RESULTS: Analysis of the pooled data from the GWAS and replication study confirmed that common PAX7 nucleotide variants are significantly associated with the increased risk of nsCL/P. The strongest individual variant was rs1339062 (c.586 + 15617T > C) with a p-value = 2.47E-05 (OR = 1.4, 95%CI: 1.20-1.64). Sequencing analysis identified a novel synonymous PAX7 substitution (c.87G > A, p.Val29Val) in a single patient with nsCLP. This transition located in the early exonic position was predicted to disrupt potential splice enhancer elements. CONCLUSION: Our study confirmed that PAX7 is a strong candidate gene for nsCL/P. Nucleotide variants of this gene contribute to the etiology of nsCL/P in the homogenous Polish population.

Association of CDKAL1 nucleotide variants with the risk of non-syndromic cleft lip with or without cleft palate.

Although the aetiology of non-syndromic cleft lip with or without cleft palate (nsCL/P) has been studied extensively, knowledge regarding the role of genetic factors in the pathogenesis of this common craniofacial anomaly is still limited. We conducted a follow-up association study to confirm that CDKAL1 nucleotide variants identified in our genome-wide association study (GWAS) for nsCL/P are associated with the risk of this anomaly. In addition, we performed a sequence analysis of the selected CDKAL1 exons. A mega-analysis of the pooled individual data from the GWAS and a replication study revealed that six out of thirteen CDKAL1 variants were positively replicated and reached the threshold of statistical significance (Ptrend < 3.85E-03). They represented a single association signal and were located within the fifth intron of CDKAL1. The strongest individual variant was rs9356746 with a Ptrend value = 5.71E-06 (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.30-1.97). Sequencing analysis did not reveal any pathogenic mutations of this gene. This study provides the first evidence that chromosomal region 6p22.3 is a novel susceptibility locus for nsCL/P. The location of the risk variants within the CDKAL1 intronic sequence containing enhancer elements predicted to regulate the SOX4 transcription may suggest that SOX4, rather than CDKAL1, is a potential candidate gene for this craniofacial anomaly.

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

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.

Association between polymorphisms at the GREM1 locus and the risk of nonsyndromic cleft lip with or without cleft palate in the Polish population.

BACKGROUND: The locus on chromosome 15q13.3 containing GREM1 is correlated with the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The aim of the present study was to find the GREM1 functional variants implicated in the aetiology of this common developmental anomaly in the Polish population. METHODS: Eight polymorphisms were genotyped in 334 NSCL/P patients and 955 controls. In addition, the GREM1 protein-coding region was sequenced in 96 NSCL/P patients. RESULTS: Significant association with a risk of oral clefts was found for 5 tested polymorphisms. The lowest p(trend) values were identified for rs16969681, rs16969816, and rs1258763 (p(trend) 4.09E-05, 3.35E-05, and 0.0002, respectively). The putative functional variant rs16969681, located in a region that has enhancer activity, was associated with a 2.6-fold lower risk for NSCL/P (odds ratio [OR] = 0.38; 95% confidence interval [CI], 0.24-0.61, p = 2.37E-05). The previously reported association of rs1258763 with NSCL/P was replicated (OR = 0.57; 95% CI, 0.44-0.73; p = 1.10E-05). For all tested GREM1 variants, no significant sex-by-genotype interaction effects were observed. The sequencing analysis did not detect any rare variants implicated in the development of oral clefts. CONCLUSION: Our results might suggest that variants influencing GREM1 expression levels, rather than variants affecting the function of the encoded protein, are significant factors in NSCL/P etiology.

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.

Nucleotide variants of the cancer predisposing gene CDH1 and the risk of non-syndromic cleft lip with or without cleft palate.

The CDH1 gene plays an important role during carcinogenesis and craniofacial morphogenesis. Germline mutations in this gene have been described in families presenting syndromic diffuse gastric cancer and orofacial clefts. The aim of this study was to evaluate the association between nucleotide variants of CDH1 and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). Six single nucleotide polymorphisms (SNPs) of the CDH1 gene (rs16260, rs9929218, rs7186053, rs4783573, rs16958383, and rs1801552) were genotyped using the TaqMan SNP genotyping assays in 250 patients with NSCL/P and 540 controls from the Polish population. Comparison between patient and control groups showed that the CDH1 rs1801552 variant, under the assumption of recessive model, was associated with a two-fold decrease in the risk of NSCL/P (ORTT vs CT + CC = 0.481, 95 % CI 0.281-0.824, p = 0.007). This association remained statistically significant even after the multiple testing correction. No significant associations with NSCL/P risk were found for the other five tested SNPs. We found a strong association between the cancer predisposing gene CDH1 and the risk of NSCL/P in the Polish population. This result, together with previous observations of co-occurrence of orofacial clefts and a variety of cancer types, suggests the need for replication studies testing rs1801552 in NSCL/P cohorts with a known cancer history.

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.

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/ß-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-3ß 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/ß-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.