Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries

Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1–5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.Fil: Shimizu, T.. Nihon University of Dentistry; JapónFil: Deeley, K.. University of Pittsburgh; Estados UnidosFil: Briseño Ruiz, J.. University of Pittsburgh; Estados UnidosFil: Faraco Junior, I. M.. University of Pittsburgh; Estados UnidosFil: Poletta, Fernando Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Brancher, J. A.. Pontifical Catholic University of Paraná; BrasilFil: Pecharki, G. D.. Pontifical Catholic University of Paraná; BrasilFil: Küchler, E. C.. Universidade Federal Fluminense; BrasilFil: Tannure, P. N.. Universidade Federal do Rio de Janeiro; BrasilFil: Lips, A.. Universidade Federal do Rio de Janeiro; BrasilFil: Vieira, T. C. S.. Universidade Federal Fluminense; BrasilFil: Patir, A.. Istanbul Medipol Universit; TurquíaFil: Yildirim, M.. Istanbul University; TurquíaFil: Mereb, J. C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Resick, J. M.. University of Pittsburgh; Estados UnidosFil: Brandon, C. A.. University of Pittsburgh; Estados UnidosFil: Cooper, M. E.. University of Pittsburgh; Estados UnidosFil: Seymen, F.. Istanbul University; TurquíaFil: Costa, M. C.. Universidade Federal do Rio de Janeiro; BrasilFil: Granjeiro, J. M.. Universidade Federal Fluminense; BrasilFil: Trevilatto, P. C.. Pontifical Catholic University of Paraná; BrasilFil: Orioli, I. M.. Universidade Federal do Rio de Janeiro; Brasil. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Castilla, Eduardo Enrique. Instituto Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Marazita, M. L.. University of Pittsburgh; Estados UnidosFil: Vieira, A. R.. University of Pittsburgh; Estados Unido

Enamel Formation Genes Influence Enamel Microhardness Before and After Cariogenic Challenge

There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes may contribute to caries. For the present study, we used DNA samples collected from 1,831 individuals from various population data sets. Single nucleotide polymorphism markers were genotyped in selected genes (ameloblastin, amelogenin, enamelin, tuftelin, and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Associations with caries experience can be detected but they are not necessarily replicated in all population groups and the most expressive results was for a marker in AMELX (p = 0.0007). To help interpret these results, we evaluated if enamel microhardness changes under simulated cariogenic challenges are associated with genetic variations in these same genes. After creating an artificial caries lesion, associations could be seen between genetic variation in TUFT1 (p = 0.006) and TUIP11 (p = 0.0006) with enamel microhardness. Our results suggest that the influence of genetic variation of enamel formation genes may influence the dynamic interactions between the enamel surface and the oral cavity. © 2012 Shimizu et al

Aquaporin 5 interacts with fluoride and possibly protects against caries

Aquaporins (AQP) are water channel proteins and the genes coding for AQP2, AQP5, and AQP6 are clustered in 12q13. Since AQP5 is expressed in serous acinar cells of salivary glands, we investigated its involvement in caries. DNA samples from 1,383 individuals from six groups were studied. Genotypes of eight single nucleotide polymorphisms covering the aquaporin locus were tested for association with caries experience. Interaction with genes involved in enamel formation was tested. The association between enamel microhardness at baseline, after creation of artificial caries lesion, and after exposure to fluoride and the genetic markers in AQP5 was tested. Finally, AQP5 expression in human whole saliva, after exposure to fluoride in a mammary gland cell line, which is known to express AQP5, and in Wistar rats was also verified. Nominal associations were found between caries experience and markers in the AQP5 locus. Since these associations suggested that AQP5 may be inhibited by levels of fluoride in the drinking water that cause fluorosis, we showed that fluoride levels above optimal levels change AQP5 expression in humans, cell lines, and rats. We have shown that AQP5 is involved in the pathogenesis of caries and likely interacts with fluoride

Enamel Formation Genes Influence Enamel Microhardness Before and After Cariogenic Challenge

Abstract There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes may contribute to caries. For the present study, we used DNA samples collected from 1,831 individuals from various population data sets. Single nucleotide polymorphism markers were genotyped in selected genes (ameloblastin, amelogenin, enamelin, tuftelin, and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Associations with caries experience can be detected but they are not necessarily replicated in all population groups and the most expressive results was for a marker in AMELX (p = 0.0007). To help interpret these results, we evaluated if enamel microhardness changes under simulated cariogenic challenges are associated with genetic variations in these same genes. After creating an artificial caries lesion, associations could be seen between genetic variation in TUFT1 (p = 0.006) and TUIP11 (p = 0.0006) with enamel microhardness. Our results suggest that the influence of genetic variation of enamel formation genes may influence the dynamic interactions between the enamel surface and the oral cavity

Erbâb-ı mütalaaya hizmet : I. Meşrutiyet kitapçılığı ve Arakel Tozluyan Efendi'nin mektupları

Donated by Klaus Kreise

Effects of Cyclosporine-Tacrolimus Switching in Posttransplantation Hyperlipidemia on High-Density Lipoprotein 2/3, Lipoprotein A1/B, and Other Lipid Parameters

Objective. In renal transplant recipients, cyclosporine treatment appears to cause more frequent hyperlipidemia than tacrolimus usage. In this study, hyperlipidemic renal transplant recipients who use cyclosporine were investigated for changes in high-density lipoprotein (HDL)-2/3, apolipoprotein (Apo) A1/B, other lipid and biochemical parameters, and body mass index after prospective cyclosporine to tacrolimus switching