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Genetics MODY diabetes
Dušátková, Petra ; Cinek, Ondřej (advisor) ; Haluzík, Martin (referee) ; Gašperíková, Daniela (referee)
The most common form of monogenic diabetes is MODY (Maturity-Onset Diabetes of the Young). It ranks among genetic defects of the β cell. It is clinically heterogenous group of disorders characterised with non insulin-dependent diabetes mellitus with autosomal dominant inheritance and age at diagnosis up to 40 years. We specified the diagnosis of MODY in more than 240 Czech families using molecular-genetic approach. The most common subtype of MODY is GCK-MODY which was proved in 376 subjects from 175 families. The risk of macrovascular complications in patiens with GCK-MODY was not detected. Additionally, we tested the ancestral origin of 4 recurrent mutations in the GCK gene causing GCK-MODY using genetic and statistical methods. We showed that three mutations (p.Glu40Lys, p.Leu315His, p.Gly318Arg) spread approximately 82-110 generations ago due to a founder effect. We also dealed with the impact of the rs560887 polymorphism on the phenotype of the patients with GCK-MODY. The genotype GG was associated with higher level of glycated haemoglobin. Analysis of patients suspect for HNF1A- or HNF4A-MODY revealed the probably first evidence of patient with HNF1A-MODY present with macrosomia and recurring ketotic hypoglycaemias in the childhood. The rare MODY genes were investigated in patients fulfilling the...
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Study of single nucleotide polymorphisms in candidate genes for Crohn's disease
Dušátková, Petra
Mgr. Petra Dušátková, Studium jednonukleotidových polymorfizmů v kandidátních genech pro Crohnovu chorobu Abstract Crohn's disease (CD) is ranked among inflammatory bowel diseases. The etiology of the disease is not completely understood yet. However, it is assumed that genetic predispositions may play important role in the etiology of CD. This work is a part of a project studying causality of single nucleotide polymorhisms within candidate genes for CD in the Czech population. We tested in total 333 patients with CD and 499 healthy subjects for SNPs: c.3020insC, p.Gly908Arg, p.Arg702Trp within the gene CARD15, g.-308G>A within the gene TNFA, p.Arg381Gln within the gene IL23R a p.Ala197Thr within the gene ATG16L1. For determination of the genotypes we used alellic discrimination in TaqMan sonds format. Variants c.3020insC, p.908Arg within the gene CARD15 were significantly associated with CD (OR = 4,4; 95%CI 3,0 - 6,4, OR = 2,7; 95%CI 1,4 - 5,0, respectively). SNP p.702Trp was associated with CD after adjustation for other two polymorphisms within the gene CARD15 (OR = 1,7; 95%CI 1,0 - 2,7). We found the protective effect of the p.381Gln in the gene IL23R (OR = 0,6; 95%CI 0,3 - 1,0). Variant p.197Ala within the gene ATG16L1 increased the risk of CD (OR = 1,3; 95%CI 1,0 - 1,9). We did not detect association...
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Genetics MODY diabetes
Dušátková, Petra ; Cinek, Ondřej (advisor) ; Haluzík, Martin (referee) ; Gašperíková, Daniela (referee)
The most common form of monogenic diabetes is MODY (Maturity-Onset Diabetes of the Young). It ranks among genetic defects of the β cell. It is clinically heterogenous group of disorders characterised with non insulin-dependent diabetes mellitus with autosomal dominant inheritance and age at diagnosis up to 40 years. We specified the diagnosis of MODY in more than 240 Czech families using molecular-genetic approach. The most common subtype of MODY is GCK-MODY which was proved in 376 subjects from 175 families. The risk of macrovascular complications in patiens with GCK-MODY was not detected. Additionally, we tested the ancestral origin of 4 recurrent mutations in the GCK gene causing GCK-MODY using genetic and statistical methods. We showed that three mutations (p.Glu40Lys, p.Leu315His, p.Gly318Arg) spread approximately 82-110 generations ago due to a founder effect. We also dealed with the impact of the rs560887 polymorphism on the phenotype of the patients with GCK-MODY. The genotype GG was associated with higher level of glycated haemoglobin. Analysis of patients suspect for HNF1A- or HNF4A-MODY revealed the probably first evidence of patient with HNF1A-MODY present with macrosomia and recurring ketotic hypoglycaemias in the childhood. The rare MODY genes were investigated in patients fulfilling the...
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Study of single nucleotide polymorphisms in candidate genes for Crohn's disease
Dušátková, Petra
Mgr. Petra Dušátková, Studium jednonukleotidových polymorfizmů v kandidátních genech pro Crohnovu chorobu Abstract Crohn's disease (CD) is ranked among inflammatory bowel diseases. The etiology of the disease is not completely understood yet. However, it is assumed that genetic predispositions may play important role in the etiology of CD. This work is a part of a project studying causality of single nucleotide polymorhisms within candidate genes for CD in the Czech population. We tested in total 333 patients with CD and 499 healthy subjects for SNPs: c.3020insC, p.Gly908Arg, p.Arg702Trp within the gene CARD15, g.-308G>A within the gene TNFA, p.Arg381Gln within the gene IL23R a p.Ala197Thr within the gene ATG16L1. For determination of the genotypes we used alellic discrimination in TaqMan sonds format. Variants c.3020insC, p.908Arg within the gene CARD15 were significantly associated with CD (OR = 4,4; 95%CI 3,0 - 6,4, OR = 2,7; 95%CI 1,4 - 5,0, respectively). SNP p.702Trp was associated with CD after adjustation for other two polymorphisms within the gene CARD15 (OR = 1,7; 95%CI 1,0 - 2,7). We found the protective effect of the p.381Gln in the gene IL23R (OR = 0,6; 95%CI 0,3 - 1,0). Variant p.197Ala within the gene ATG16L1 increased the risk of CD (OR = 1,3; 95%CI 1,0 - 1,9). We did not detect association...
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