Systemic Lupus Erythematosus (SLE) is an autoimmune disease that targets the vascular system, and can result in premature atherosclerotic vascular disease. The causes of SLE and many of the SLE associated problems, such as thrombosis, anitphospholipid syndrome, and atherosclerosis, which are significant public health concerns, are thought to be multifactorial, or caused by interactions of many environmental and genetic factors. Several genes have been proposed and studied in conjunction with these manifestations. This study focuses on one of these genes, apolipoprotein H (APOH gene, beta-2-GPI protein). The effects of several polymorphisms within the coding region in the APOH gene have been studied; however, possible effects of the single nucleotide polymorphisms (SNPs) within the promoter region have not been characterized. In this study, 6 SNPs in the APOH promoter were genotyped in 381 SLE women and 497 healthy women controls. This study aimed to determine the association of these polymorphisms with the occurrence of SLE, with the plasma levels of beta-2-GPI, and with the presence of antiphospholipid antibodies (APA). It was hypothesized that the genetic variation in the promoter region of the APOH gene may affect the risk of SLE and may do so through an effect on plasma beta-2-GPI levels or through its influence on APA. Among whites, the risk of SLE was modestly affected by the -1219 SNP (p = 0.057). While in blacks, the -759 SNP (p = 0.022) and the -700 SNP (p = 0.035) showed association with SLE. The haplotype pattern in whites was associated with SLE risk (p = 0.00015). The -643 SNP showed a modest effect on plasma beta-2-GPI levels in white SLE cases (p = 0.096) and black controls (p = 0.081). Significant differences were seen between antibody negative and all antibody positive groups in whites for the -1284 SNP (p = 0.02) and the -759 SNP (p = 0.046). These results suggest that genetic variation in the APOH promoter may affect SLE risk, beta-2-GPI levels, and the occurrence of antiphospholipid antibodies.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04142005-172749 |
| Date | 20 June 2005 |
| Creators | Jacobs, Erin Lynn |
| Contributors | Clareann Bunker, Candace Kammerer, M. Ilyas Kamboh |
| 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-04142005-172749/ |
| 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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