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ENVIRONMENTAL RISK FACTORS OF MULTIPLE SCLEROSIS: A TWIN STUDY by Khandaker Talat Shamsul Islam A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (EPIDEMIOLOGY) May 2007 Copyright 2007 Khandaker Talat Shamsul Islam
Object Description
Title | Environmental risk factors of Multiple Sclerosis: a twin study |
Author | Islam, Khandaker Talat Shamsul |
Author email | islam@usc.edu |
Degree | Doctor of Philosophy |
Document type | Dissertation |
Degree program | Epidemiology |
School | Keck School of Medicine |
Date defended/completed | 2007-03-14 |
Date submitted | 2007 |
Restricted until | Unrestricted |
Date published | 2007-04-02 |
Advisor (committee chair) | Mack, Thomas M. |
Advisor (committee member) |
Gilliland, Frank D. Gauderman, W. James Cozen, Wendy Weiner, Leslie P. |
Abstract | Multiple sclerosis (MS) is an autoimmune mediated degenerative disease of the central nervous system that is characterized by focal neurological deficits that are marked by temporal and spatial variation. It is a debilitating disease affecting the young adults with a propensity for female and Whites. Beside the latitude gradient, female sex and familial risk, little is known about the risk factors of MS and even less regarding its etiology. Increased recurrence risk among 1st degree relatives and twins of an MS case underscores the importance of genetic susceptibility in MS. However, the observed of ~20% recurrence risk among co-twin of monozygotic twins provides a great insight to MS risk as 1) it is 400 times more than the lifetime risk of general population but 2)80% of the co-twins despite having the same genetic risk do not get the disease. Thus the genetic susceptibility appears to be a necessary but not a sufficient risk factor for MS. Identifying environmental risk factors for MS can greatly reduce the burden of the disease. That have been the focus of my research. My interest is to know the relationship between environmental and genetic risk factors and identify specific risk/protective factors of MS. I addressed my research questions in a large population (~1200) twins with at least one case of MS. The twins represented MS cases among twins in the North American population from 1980-1992. Comparing pairwise concordance rate among monozygotic (MZ) and same-sex dizygotic (DZ) twins by latitude of birthplace I identified the importance of gene-environmental interaction in MS risk and showed that the variation in concordance rate mimics the latitude gradient in MS which can be explained by environmental and genetic risk factors. Limiting our analysis to MZ twins we observed that sun exposure during childhood is associated with reduction in the risk of MS. The protective effect of sun exposure might vary by gender and HLA status.; As the protective effect of sun exposure can be mediated through vitamin D status, I further plan to investigate the role of genes involved in vitamin D pathway in MS. |
Keyword | Multiple Sclerosis; twin study; environmental risk factors |
Language | English |
Part of collection | University of Southern California dissertations and theses |
Publisher (of the original version) | University of Southern California |
Place of publication (of the original version) | Los Angeles, California |
Publisher (of the digital version) | University of Southern California. Libraries |
Type | texts |
Legacy record ID | usctheses-m343 |
Contributing entity | University of Southern California |
Rights | Islam, Khandaker Talat Shamsul |
Repository name | Libraries, University of Southern California |
Repository address | Los Angeles, California |
Repository email | cisadmin@lib.usc.edu |
Filename | etd-Islam-20070402 |
Archival file | uscthesesreloadpub_Volume26/etd-Islam-20070402.pdf |
Description
Title | Page 1 |
Contributing entity | University of Southern California |
Repository email | cisadmin@lib.usc.edu |
Full text | ENVIRONMENTAL RISK FACTORS OF MULTIPLE SCLEROSIS: A TWIN STUDY by Khandaker Talat Shamsul Islam A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (EPIDEMIOLOGY) May 2007 Copyright 2007 Khandaker Talat Shamsul Islam |