title: Genetic and functional analyses of MRAS and HNF1A genes in diabetes and diabetic nephropathy.
abstract: Evidence has recently indicated that the           MRAS and HNF1A genetic polymorphisms are associated           with coronary artery disease. The MRAS           and HNF1A genes are located on chromosomes 3q           and 12q within the regions where associations with           diabetes and diabetic nephropathy occur. We thus           performed genetic and functional analyses of these           two genes to evaluate their impacts on diabetes and           diabetic nephropathy. MRAS and HNF1A genetic           polymorphisms were genotyped in 1399 Czech subjects           including non-diabetic controls (339), type 1           (243) and type 2 (817) diabetic patients with and           without diabetic nephropathy using TaqMan allelic           discrimination. Gene expression levels in the kidneys           of diabetic Goto-Kakizaki and Wistar rats were detected           with real-time RT-PCR. Despite no significance           in genetic analysis of diabetic subjects, SNP           rs2259816 in the HNF1A gene tended to associate with diabetic nephropathy in type 1 diabetic patients.           The hnf1a gene expression was significantly decreased           in kidney tissues of Goto-Kakizaki rats compared           to Wistar and insulin-treated Goto-Kakizaki           rats. There was neither significant association in the           MRAS genetic polymorphism with diabetic nephropathy           nor variation of mras gene expression in the kidneys           of Goto-Kakizaki and Wistar rats. Data from           the present study have not proved any significant association           of the MRAS and HNF1A genetic polymorphisms           with diabetes and diabetic nephropathy in a           cohort of Czech population. However, the functional           analysis and the trend in genetic analysis suggest           that the HNF1A gene may have primary genetic impact           on the development of diabetic nephropathy.
authors: Third Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic. eva.horova@email.cz
authors: E
authors: E
authors: Horová
authors: M
authors: M
authors: Prázný
authors: K
authors: K
authors: Kaňková
authors: K
authors: K
authors: Brismar
authors: H F
authors: HF
authors: Gu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005838:Genotype; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000235:genetics*
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; C109523:MRAS protein, human; D018631:ras Proteins