Associations Between Genetic Variants in Mrna Splicing-Related Genes and Risk of Lung Cancer: a Pathway-Based Analysis from Published Gwass

mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of thisprocess may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summarydata from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancerof the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The sixnovel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression inlymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shednew light on the role of mRNA splicing genes in the development of lung cancer

Block iliac bone grafting enhances osseous healing of alveolar reconstruction in older cleft patients : a radiological and histological evaluation

Older alveolar cleft patients (&12 years old) often have wide bone defect as well as teeth loss, resulting in poor osseous healing with conventional alveolar bone grafting (ABG). In this study, we investigated a surgical technique of block iliac bone grafting for the alveolar cleft reconstruction and evaluated the clinical and radiological outcomes of these cleft patients. Fifteen patients were included in this study. All cases received preoperative cone bean computed tomography (CBCT) scans for the alveolar cleft evaluation. Osseous outcomes of block iliac bone grafting were assessed at 1 week, 3- and 6-month postoperatively. Volume changes and bone resorption rates were calculated using the measurement modules of Simplant software. Bone samples from one patient undergoing dental implantation were assessed by micro-CT and histological examination. The morbidities of donor-site were analyzed by clinical examination and questionnaire survey. The average age of the case series was 18.53±2.50 years. The intraoral incision of thirteen cases healed well. However, two cases had oronasal fistula and graft exposure at 1-week postoperatively. The results of follow-up CBCT scans showed significant resistance to radiation on both sides of the bone graft, suggesting a good osseous healing and new bone formation. The mean residual bone volume was 1.68±0.26 cm3, 1.29±0.23 cm3 and 1.15±0.23 cm3 at 1-week, 3- and 6-month postoperatively. Correspondingly, the mean bone resorption rates in 3- and 6-month postoperative were 21.78±6.88% and 30.66±8.97%, respectively. From micro-CT and HE examinations, the block bone samples exhibited a cancellous structure in which mature bone trabecula and functional blood vessels appeared. The average scores of donor-site morbidities were drastically decreased at 3- and 6-month postoperatively compared with those at 1-week postoperatively. Our results demonstrated that block iliac bone grafting could achieve satisfying osseous outcomes in older alveolar cleft patients, and this technique provided favorable bony condition for further treatments, especially dental implantation

Evaluating the effect of digital technology on the learning of orthodontic cephalometric measurement

Background: This study aimed to evaluate the effect of applying digital technology in cephalometric measurement teaching and students’ acceptance towards it. Methods: In total, 94 undergraduates of stomatology were recruited and randomly allocated to two groups. According to the cross-over design, both groups completed cephalometric measurements through the traditional hand-drawn method and digital technology (the Dolphin software) in different orders. By traditional hand-drawn method, students need to depict the outlines of the craniofacial anatomical structures on the sulfuric transfer paper first, then marked the measurement points and completed the measurement of line spacings and angles. By digital technology, they should mark the points in the software and adjust the automatically generated outlines of the structures and obtained the results. Besides, an online questionnaire was designed to investigate students' attitudes toward the digital technology. Two professional orthodontists were invited as instructors. They measured a lateral cranial radiograph by two methods with one week’s interval, and their intra- and inter-class correlation coefficient were measured. The means of their measurements were set as standards. Results: The inter- and intra-ICC of two instructors surpassed 90%, and there were no significant differences between their measurements, and the measurements by two methods. There were significant differences of students’ measurements (P 1-SNA&lt;0.01, P 1-SNB=0.01 and P 1-L1-NB (mm)&lt;0.01; SNA: sella-nasion-subspinale angle, SNB: sella-nasion-supramental angle, L1-NB (mm): the distance from the lower central incisor tip to the nasion-supramental plane) between the traditional method and digital technology. Besides, the most results of digital technology were closer to the standards than those of traditional method, including five items with statistical significance (P 2-SNB&lt;0.05, P 2-L1-NB (mm)&lt;0.01, P 2-FMA&lt;0.05, P 2-FMIA&lt;0.05, P 2-IMPA&lt;0.01), while three items were the opposite (P 2-SNA&lt;0.05, P 2-ANB (mm)&lt;0.01, P 2-NA-PA&lt;0.01). The questionnaire showed more students preferred digital technology (33%) compared with traditional method (2%) and 72% of participants mastered 50-80% of cephalometric knowledge after the course.</p

Evaluating the effect of digital technology on the learning of orthodontic cephalometric measurement [version 3; peer review: 2 approved]

Background: This study aimed to evaluate the effect of applying digital technology in orthodontic learning, students' new skills and satisfaction towards it. Methods: In total, 94 undergraduates of stomatology were recruited and randomly allocated to two groups. According to the cross-over design, both groups completed cephalometric measurements through the traditional hand-drawn method and digital technology (the Dolphin software) in different orders. By traditional hand-drawn method, students need to depict the outlines of the craniofacial anatomical structures on the sulfuric transfer paper first, then marked the measurement points and completed the measurement of line spacings and angles. By digital technology, they should mark the points in the software and adjust the automatically generated outlines of the structures and obtained the results. Besides, an online questionnaire was designed to investigate students' attitudes toward the digital technology. Two professional orthodontists were invited as instructors. They measured a lateral cranial radiograph by two methods with one week’s interval, and their intra- and inter-class correlation coefficient were measured. The means of their measurements were set as standards. Results: The inter- and intra-ICC of two instructors surpassed 90%, and there were no significant differences between their measurements, and the measurements by two methods. There were significant differences of students’ measurements (P 1-SNA<0.01, P 1-SNB=0.01 and P 1-L1-NB (mm)<0.01) between the traditional method and digital technology. Besides, the most results of digital technology were closer to the standards than those of traditional method, including five items with statistical significance (P 2-SNB<0.05, P 2-L1-NB (mm)<0.01, P 2-FMA<0.05, P 2-FMIA<0.05, P 2-IMPA<0.01), while three items were the opposite (P 2-SNA<0.05, P 2-ANB (mm)<0.01, P 2-NA-PA<0.01). The questionnaire showed more students preferred digital technology compared with traditional method and 72% of participants mastered 50-80% of cephalometric knowledge after the course

Up-regulation of multiple proteins and biological processes during maxillary expansion in rats

<p>Abstract</p> <p>Background</p> <p>Maxillary expansion (ME) is a common practice in orthodontics that aims to increase the constricted maxillary arch width. Relapse often occurs, however, and better treatment strategies are needed. In order to develop a more effective method, this study was designed to further examine the process of tissue remodeling during ME, to identify the changes in expression of several proteins of interest, and to clarify the molecular mechanism responsible for tissue remodeling.</p> <p>Methods</p> <p>Male Wistar rats were randomly divided into control and ME groups. The rats were euthanized at various intervals over 11 days, and the dissected palates were prepared for histological examination. The structure of the midpalatal sutures changed little during the first three days. Proteins from samples in the ground midpalatal tissues obtained on the third day were subjected to two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. Validation of protein expression was performed by Western blot analyses.</p> <p>Results</p> <p>From day 5, chondrocytes in the inner layer of suture cartilage and osteoblasts at the end of the suture cartilage began to proliferate, and the skeletal matrix increased later adjacent to the cartilage in the ME group. Comparative proteomic analysis showed increases in 22 protein spots present in the ME group. The changes in three proteins closely related to osteogenesis (parathyroid hormone, osteoprotegerin and vimentin) were confirmed by Western blotting.</p> <p>Conclusion</p> <p>Many proteins are over-expressed during ME, and they may play an important role in the remodeling process.</p

Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: a pathway-based analysis from published GWASs

mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summary data from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6 and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The six novel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression in lymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shed new light on the role of mRNA splicing genes in the development of lung cancer

Genome- and Transcriptome-Wide Association Studies Identify Susceptibility Genes and Pathways for Periodontitis

Several genes associated with periodontitis have been identified through genome-wide association studies (GWAS); however, known genes only explain a minority of the estimated heritability. We aimed to explore more susceptibility genes and the underlying mechanisms of periodontitis. Firstly, a genome-wide meta-analysis of 38,532 patients and 316,185 healthy controls was performed. Then, cross- and single-tissue transcriptome-wide association studies (TWAS) were conducted based on GWAS summary statistics and the Genotype-Tissue Expression (GTEx) project. Risk genes were evaluated to determine if they were differentially expressed in periodontitis sites compared with unaffected sites using public datasets. Finally, gene co-expression network analysis was conducted to identify the functional biology of the susceptible genes. A total of eight single nucleotide polymorphisms (SNPs) within the introns of lncRNA LINC02141 approached genome-wide significance after meta-analysis. EZH1 was identified as a novel susceptibility gene for periodontitis by TWAS and was significantly upregulated in periodontitis-affected gingival tissues. EZH1 co-expression genes were greatly enriched in the cell-substrate junction, focal adhesion and other important pathways. Our findings may offer a fundamental clue for comprehending the genetic mechanisms of periodontitis

Genome- and Transcriptome-Wide Association Studies Identify Susceptibility Genes and Pathways for Periodontitis

Several genes associated with periodontitis have been identified through genome-wide association studies (GWAS); however, known genes only explain a minority of the estimated heritability. We aimed to explore more susceptibility genes and the underlying mechanisms of periodontitis. Firstly, a genome-wide meta-analysis of 38,532 patients and 316,185 healthy controls was performed. Then, cross- and single-tissue transcriptome-wide association studies (TWAS) were conducted based on GWAS summary statistics and the Genotype-Tissue Expression (GTEx) project. Risk genes were evaluated to determine if they were differentially expressed in periodontitis sites compared with unaffected sites using public datasets. Finally, gene co-expression network analysis was conducted to identify the functional biology of the susceptible genes. A total of eight single nucleotide polymorphisms (SNPs) within the introns of lncRNA LINC02141 approached genome-wide significance after meta-analysis. EZH1 was identified as a novel susceptibility gene for periodontitis by TWAS and was significantly upregulated in periodontitis-affected gingival tissues. EZH1 co-expression genes were greatly enriched in the cell-substrate junction, focal adhesion and other important pathways. Our findings may offer a fundamental clue for comprehending the genetic mechanisms of periodontitis

Expression Quantitative Trait Locus Study of Non-Syndromic Cleft Lip with or without Cleft Palate GWAS Variants in Lip Tissues

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disease with a strong genetic component. More than 40 loci have been identified to be associated with the risk of NSCL/P by genome-wide association studies (GWASs), but the majority of these variants are mapped to non-coding regions of the genome. Expression quantitative trait locus (eQTL) studies have increasingly been integrated with GWASs to identify target genes for these non-coding variants. In this study, we generated a unique, lip-specific eQTL dataset from 40 NSCL/P patients. A total of 5158 eQTL SNPs (eSNPs) -689 eQTL genes were identified after multiple corrections. Then, we integrated nominal eQTL SNPs with NSCL/P risk SNPs and identified 243 variants associated with the expression of 18 genes in lip tissues. Functional annotation analysis indicated that these risk eSNPs were significantly enriched in transcription regulation and chromatin open regions on the genome. These susceptible genes were enriched in cell fate determination, the pluripotency of stem cells, and Wnt signaling pathways. Finally, 8 of the 18 susceptible genes were differentially expressed in NSCL/P case-control studies. In summary, we have generated a unique lip-specific eQTL resource and identified multiple associations for NSCL/P risk loci, which should inform functional studies of NSCL/P biology

Association between MMP-1 g.-1607dupG polymorphism and periodontitis susceptibility: a meta-analysis.

BACKGROUND: Matrix metalloproteinase-1 (MMP-1) plays an important role during the destruction of periodontal tissue. Although multiple studies had focused on the association between MMP-1 g.-1607dupG and periodontitis susceptibility, the results remained inconclusive. The purpose of this meta-analysis was to explore its role in the development of periodontitis. METHODS: Retrieved studies from Pubmed, Web of Science, Medline and Google Scholar Search regarding MMP-1 g.-1607dupG and periodontitis susceptibility were included into the final analysis with definite selection and exclusion criteria. Overall and stratified analyses based on disease type, severity, ethnicity and smoking status were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between MMP-1 g.-1607dupG and periodontitis susceptibility, while Q test and Egger's test were adopted respectively to assess heterogeneity among studies and publication bias. RESULTS: A total of 1580 periodontitis cases and 1386 controls in 11 case-control studies were included in the meta-analysis. The pooled results showed significant association between periodontitis susceptibility and MMP-1 g.-1607dupG polymorphism in homozygote (2G/2G versus 1G/1G, OR = 1.50, 95% CI = 1.02-2.20) and dominant model analysis (2G/2G+2G/1G versus 1G/1G, OR = 1.28, 95% CI = 1.04-1.57). For subgroups by type of periodontitis, increased risk of chronic periodontitis was observed on heterozygote (2G/1G versus 1G/1G, OR = 2.01, 95% CI = 1.58-2.56) and dominant model (OR = 1.27, 95% CI = 1.03-1.57). Furthermore, similar association was also detected in severe chronic periodontitis (2G/2G versus 1G/1G, OR = 2.15, 95% CI = 1.35-3.43; 2G/2G+2G/1G versus 1G/1G, OR = 1.64, 95% CI = 1.12-2.39; 2G/2G versus 2G/1G+1G/1G, OR = 1.86, 95% CI = 1.31-2.64). CONCLUSIONS: Our meta-analysis demonstrated that MMP-1 g.-1607dupG polymorphism was associated with chronic periodontitis, especially the severity of the disease condition