Type 1 diabetes mellitus is a multifactorial autoimmune disease caused by a combination of genetic and environmental factors. Further knowledge and understanding about the genes which play a role in type 1 diabetes has a clear public health significance in that it will aid in the prediction, treatment and a possible cure. Type 1 diabetes is a chronic disease with a lengthy preclinical course, which eventually results in pancreatic beta cell destruction and inability of the body to produce insulin hormone. Type 1 diabetic patients generally require exogenous insulin to survive. Several genetic loci have been proposed to be linked to type 1 diabetes; however, the HLA and VNTR regions are currently believed to account for the majority of genetic risk, contributing to about 42% and 10% of an individuals risk to develop type 1 diabetes, respectively. This study focuses on the candidate gene Islet Cell Autoantigen 1 (ICA1), which codes for the protein ICA69. This protein product is expressed in the islets of Langerhans, the neuroendocrine system and in the thymic medulla; this last location is an area of the body known to play a major role in immunologic tolerance. Preliminary studies in the NOD and B6 mouse models suggest that a SNP within the promoter region of Ica1 affects transcription and may account for altered expression in the thymus. Our current study aimed to determine whether single nucleotide polymorphisms within intronic regions of the human ICA1 gene differed between a diabetic case population and non-diabetic controls. It was hypothesized that SNPs within the ICA1 gene differ between cases and controls and play a role in the onset of type 1 diabetes. Polymerase Chain Reaction (PCR) was applied for DNA amplification and the pyrosequencing technique was used to genotype all samples. At SNP location rs2058519 there was a clear genotypic difference between the cases and controls (p= .0003). These results suggest that genetic variation at this specific SNP location in the ICA1 may be associated with type 1 diabetes susceptibility. The ultimate goal of this study is to determine whether our candidate gene ICA1 appears to play a role in the pathogenesis of type 1 diabetes.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04102006-140611 |
| Date | 01 June 2006 |
| Creators | Blout, Carrie Lynn |
| Contributors | Elizabeth Gettig, MS, CGC, Michael M. Barmada, Ph.D., John W. Wilson, PhD, Massimo Pietropaolo, M.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04102006-140611/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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