To characterise type 2 diabetes (T2D) associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promising association signals were followed-up in additional data sets (of 14,545 or 7,397 T2D cases and 38,994 or 71,604 controls). We identified 13 novel T2D-associated loci (p<5×10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common SNVs. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion, and in adipocytes, monocytes and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.

Aim: The aims of this study were to validate a randomized, split‐mouth, localized experimental gingivitis model and to identify subjects with different gingivitis susceptibility. Material and Methods: In each of 96 healthy subjects, one maxillary quadrant was randomly assigned as “test” (experimental gingivitis) and the contralateral quadrant as “control”. Plaque index (PlI), gingival index (GI), gingival crevicular fluid volume (GCF), and angulated bleeding score (AngBS) were recorded in both quadrants at days 0, 7, 14, and 21. Cumulative plaque exposure (CPE), i.e. PlI over time, was calculated. Day‐21 GCF was standardized according to CPE, and residuals of GCF on CPE were calculated. Two subpopulations were then defined, based on upper and lower quartiles of GCF‐residual distribution and were, respectively, identified as “high‐responder” (HR; n=24) and “low‐responder” (LR; n=24). Results: At test quadrants, all parameters significantly increased throughout the trial, while in control quadrants, PlI, GI, and AngBS remained low. Significant differences were noted between test and control quadrants on days 7, 14, and 21 for all parameters. Significant increases in GI, AngBS, and GCF were observed in test quadrants over the course of the study in both HR and LR groups. Significant differences were noted between HR and LR groups for all gingivitis parameters on day 21 in test quadrants, without any significant differences in PlI or CPE between the groups. Conclusions: We identified two subpopulations characterized by significant differences in clinical parameters of plaque‐induced gingival inflammation, despite similar amounts of plaque deposits and plaque accumulation rates.

Previous candidate genes carry no susceptibility factors for AgP. Association of IL-10 rs61815643 with AgP is suggested. ANRIL is associated with periodontitis across different populations.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.

Twenty-four (24) deep wide buccal gingival recessions were treated with ePTFE membrane according to guided tissue regeneration principles (GTR). Factors affecting the surgical outcome of the regenerative procedure were retrospectively analyzed. In 16 cases, the barrier membrane was used in conjunction with tetracycline root conditioning and fibrin-fibronectin system application, and 8 cases were treated with the membrane alone. Healing response was evaluated 12 months after surgery. Since no difference was observed between the two treatment protocols, all available data were grouped. Mean recession depth was reduced from 4.6 mm to 1.3 mm postoperatively, which represents an average root coverage of 71.7%. Fifty percent (50%) of the cases showed clinical attachment gain greater than or equal to 4 mm and a mean increase of keratinized tissue of 1.0 mm was observed. Baseline recession depth and extent of membrane exposure at the reentry procedure significantly influenced the amount of newly-formed tissue under the membrane. Recession reduction positively correlated with the preoperative recession depth and the regenerated tissue gain. Treatment was also affected by tooth location, recession reduction, and attachment gain, being significantly greater in upper than lower archs. Results suggest that GTR technique represents a predictable procedure to improve the soft tissue conditions of deep mucogingival defects. Randomized controlled trials of other forms of management of mucogingival defects as compared to the GTR technique will be necessary to fully evaluate the utility of the GTR technique.