Type 1 diabetes mellitus (T1D) is a disease of major public health concern as it is one of the most common diseases of childhood and costs millions of dollars in health care each year in the U.S. T1D is an autoimmune disease and is caused by multiple factors including genetics, autoimmunity, and environment. The genetics of T1D is complex as there are multiple genes thought to play a role in its susceptibility, with the best defined risks associated with the HLA-DQ molecule. This study analyzes the role of the DQ molecule in 265 diabetic children and 1000 unaffected first degree relatives in order to further support the current literature of the presence of specific DQ alleles and haplotypes with a large representative sample from the U.S.
In the diabetic probands, the analysis was supported by the previous literatures for the presence of non-Asp 57 alleles but not for the presence of the DQ2 and DQ8 haplotypes. In this study, 94.14% (96.65% including the DR2 group) have at least one non-Asp allele with a breakdown of 30.54% as non-Asp/Asp (33.05% including DR2) and 63.60% with non-Asp/non-Asp, and 6% Asp/Asp. The distribution of the DQ2 and DQ8 haplotypes includes, 78.63% possessing DQ2 and/or DQ8 haplotypes with 6.49% as DQ2 homozygotes (DQ2/DQ2), 4.96% as DQ8 homozygotes (DQ8/DQ8), and 16.79% as DQ2/DQ8 heterozygotes. These figures are only slightly higher when looking at the Caucasians or the individuals with younger ages of onset. These unexpected results may be the result of clinical or ethnic variability in the population, however further investigation is warranted.
While there is limited information available of the non-Asp alleles and DQ2 and DQ haplotypes for first degree relatives, the results in the study seem to be supported both by previous studies and on the risks associated with each haplotype. Results show that 33.59% non-Asp/non-Asp, 58.2% Asp/non-Asp (with 14.55% of these individuals non-Asp/0602 specifically), and 8.21% Asp/Asp. In the DQ2 and DQ8 analysis 68.34% had DQ2 and/or DQ8 haplotypes, with 31.94% as DQ2 homozygotes or heterozygotes, 30.11% were either DQ8 homozygous or heterozygous, and 6.31% were DQ2/DQ8 heterozygotes.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04132007-163327 |
| Date | 27 June 2007 |
| Creators | Smolnik, Brandy Marie |
| Contributors | Dorothy J. Becker, Vincent Arena, Elizabeth Gettig |
| 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-04132007-163327/ |
| 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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