Molecular-genetic Study of Polygenic Diseases with a Special Focus on Diabetes Mellitus

Mgr. Pavlína Čejková MOLECULAR-GENETIC STUDY OF POLYGENIC DISEASES WITH A SPECIAL FOCUS ON DIABETES MELLITUS Abstract Polygenic diseases with complex mode of inheritance constitute an increasing public health burden. The aim of this study was to contribute to our current knowledge in genetic background of several complex diseases, namely enteropathy-type T-cell lymphoma, type 1 and type 2 diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis a psoriatic arthritis, in order to better understand the pathogenesis of the diseases with potential diagnostic, prognostic or therapeutic applications. In the ETL, previously detected gain in chromosome band 9q was further narrowed down by microsatellite analysis to 9q34, and gDNA-based quantitative PCR confirmed amplification of both, ABL1 and NOTCH1genes. HLA genotyping of T1D manifested in childhood, adult-onset T1D and LADA showed partially different genetic predispositions. This finding points out a possible role of environmental factors that increases with age, and at least partly different immunogenetic etiology between autoimmune DM manifested in children and in adults. Further, there is some evidence that T1D and LADA diabetes susceptibility may slightly differ as indicated by different frequencies of HLA and NFKBIA gene polymorphisms. This..