title: Structural Properties of Gene Promoters Highlight More than Two Phenotypes of Diabetes.
abstract: Genome-wide association studies (GWAS) published in the last decade raised the number of loci associated with type 1 (T1D) and type 2 diabetes (T2D) to more than 50 for each of these diabetes phenotypes. The environmental factors seem to play an important role in the expression of these genes, acting through transcription factors that bind to promoters. Using the available databases we examined the promoters of various genes classically associated with the two main diabetes phenotypes. Our comparative analyses have revealed significant architectural differences between promoters of genes classically associated with T1D and T2D. Nevertheless, five gene promoters (about 16%) belonging to T1D and six gene promoters (over 19%) belonging to T2D have shown some intermediary structural properties, suggesting a direct relationship to either LADA (Latent Autoimmune Diabetes in Adults) phenotype or to non-autoimmune type 1 phenotype. The distribution of these promoters in at least three separate classes seems to indicate specific pathogenic pathways. The image-based patterns (DNA patterns) generated by promoters of genes associated with these three phenotypes support the clinical observation of a smooth link between specific cases of typical T1D and T2D. In addition, a global distribution of these DNA patterns suggests that promoters of genes associated with T1D appear to be evolutionary more conserved than those associated with T2D. Though, the image based patterns obtained by our method might be a new useful parameter for understanding the pathogenetic mechanism and the diabetogenic gene networks.
authors.affiliation: National Institute of Diabetes, Nutrition and Metabolic Diseases "N.C. Paulescu", Bucharest, Romania.
authors.forename: Constantin
authors.initials: C
authors.lastname: Ionescu-Tîrgovişte
authors.affiliation: National Institute of Diabetes, Nutrition and Metabolic Diseases "N.C. Paulescu", Bucharest, Romania; National Institute of Pathology "Victor Babes", Bucharest, Romania; Department of Genetics, University of Bucharest, Aleea Portocalelor 1-3, Sector 6, Bucharest, Romania.
authors.forename: Paul Aurelian
authors.initials: PA
authors.lastname: Gagniuc
authors.affiliation: National Institute of Diabetes, Nutrition and Metabolic Diseases "N.C. Paulescu", Bucharest, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Guja
mesh_terms: D001483:Base Sequence; D003920:Diabetes Mellitus / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics*