Non-syndromic cleft lip with palate (NSCLP) is the most serious sub-phenotype of non-syndromic orofacial clefts (NSOFC), which are the most common craniofacial birth defects in humans. Here we conduct a GWAS of NSCLP with multiple independent replications, totalling 7,404 NSOFC cases and 16,059 controls from several ethnicities, to identify new NSCLP risk loci, and explore the genetic heterogeneity between sub-phenotypes of NSOFC. We identify 41 SNPs within 26 loci that achieve genome-wide significance, 14 of which are novel (RAD54B, TMEM19, KRT18, WNT9B, GSC/DICER1, PTCH1, RPS26, OFCC1/TFAP2A, TAF1B, FGF10, MSX1, LINC00640, FGFR1 and SPRY1). These 26 loci collectively account for 10.94% of the heritability for NSCLP in Chinese population. We find evidence of genetic heterogeneity between the sub-phenotypes of NSOFC and among different populations. This study substantially increases the number of genetic susceptibility loci for NSCLP and provides important insights into the genetic aetiology of this common craniofacial malformation.

Objective. Curcumin, an active ingredient of turmeric, is proved to be a potential candidate of controlling inflammation and bone resorption, but few reports are on the periodontitis. The purpose of this study was to evaluate whether the intra-gastric administration of curcumin could inhibit the inflammation and alveolar bone resorption in rats following ligature-induced experimental periodontitis. Materials and method. Male Wistar rats were randomly divided into three groups: no ligature placement and administration of vehicle, ligature placement and administration of vehicle, ligature placement and administration of curcumin. After the animals were sacrificed, their mandibles were collected for morphological, histological and immunohistochemical analysis; their gingival tissues were collected for cytokine measurements. Results. Bone resorption was significantly higher in the experimental periodontitis animals treated with vehicle compared with the curcumin-treated group or the control group. Furthermore, receptor activator of nuclear factor-κB ligand (RANKL), receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels were higher in the experimental periodontitis animals treated with vehicle compared with the curcumin treated group or the control group. Conclusions. Curcumin may decrease alveolar bone loss in the experimental periodontitis rats via suppressing the expression of RANKL/RANK/OPG and its anti-inflammatory properties.

Background: Dentin phosphoprotein (DPP) is the most abundant non-collagenous protein in dentin, which is highly phosphorylated and plays key roles in dentin biomineralisation. The aetiology of isolated hereditary dentin disorders in most affected families is largely unknown and the association between DPP and dentin disorders has not been well established. This study aims to determine whether there are some involvements for DPP mutations in inherited dentin disorders and to clarify the sequence variation patterns of DPP in normal population. Methods: Genomic DNA was analysed in eight families with hereditary dentin disorders and 110 individuals in the normal population. The full coding sequence of DPP was amplified by polymerase chain reaction (PCR) and screened for mutations and variations by direct sequencing and TOPO TA-cloning sequencing. Results: Five frameshift mutations in DPP coding region were identified in five of the eight families. The mutations co-segregated with the disease phenotypes in affected families and were not found in 220 control chromosomes. In the normal population, we revealed 14 in-frame indels (insertion/deletion), six non-synonymous single nucleotide polymorphisms (SNPs), and five synonymous SNPs in the DPP coding region. These variants display extensive linkage disequilibrium and constitute a total of 15 haplotypes with three predominant haplotypes in the investigated normal population. Conclusions: Our data provide the first evidence that DPP mutations can cause hereditary dentin disorders and suggest that in-frame length variations and missense SNPs in DPP have no obvious pathogenetic effects on dentin formation.