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Genetic Variation in the Paraoxonase-1 Gene and Association with Systemic Lupus Erythematosus

Tripi, Laura Margaretha (2005) Genetic Variation in the Paraoxonase-1 Gene and Association with Systemic Lupus Erythematosus. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting approximately one million individuals in the United States. Individuals with lupus are at an extremely increased risk (up to 50-fold) to develop coronary heart disease (CHD) compared to the general population. Traditional risk factors are insufficient to explain the increase in risk. The presence of anti-phospholipid antibodies (seen at a higher rate in SLE patients than in the general population) is suspected to play a role. CHD is the leading cause of death for both men and women of all ethnic groups in the United States. Understanding the genetic causes of CHD in high risk populations, such as individuals with SLE, can help facilitate the understanding of CHD in the general population. Due to the large public health significance of CHD, investigating the contributing factors and disease etiology could have a major impact on risk assessment and possible treatment of CHD. One gene involved in lipid metabolism, a major part of the development of atherosclerotic plaques and CHD, is paraoxonase-1 (PON1). PON1 encodes the enzyme paraoxonase, which inhibits the oxidation of low density lipoprotein (LDL) to help prevent its uptake by macrophages, thereby reducing the incidence of atherosclerotic plaques. Eight genetic variants in the PON1 gene were examined to determine their impact on SLE disease status, the presence of anti-phospholipid antibodies (APA), and PON activity. Polymorphisms in PON1 were not found to have a significant impact on SLE disease status or the presence of APA, however three of the polymorphisms studied were found to have a significant impact on PON activity. While SLE and CHD are complex diseases, likely resulting from gene-gene and gene-environment interactions, the identification of these associations between PON1 polymorphisms and PON activity may help to clarify the role of PON in CHD development and possibly lead to more accurate risk assessment and/or the investigation of treatment options for this common disease.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tripi, Laura Margarethalaura.tripi@mail.hgen.pitt.edu
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKamboh, M Ilyasilyas.kamboh@mail.hgen.pitt.eduKAMBOH
Committee MemberKammerer, Candacecandace.kammerer@mail.hgen.pitt.eduCMK3
Committee MemberBunker, Clareannbunkerc@pitt.eduBUNKERC
Date: 23 June 2005
Date Type: Completion
Defense Date: 8 April 2005
Approval Date: 23 June 2005
Submission Date: 14 April 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: atherosclerosis; lipid metabolism; pon; single nucleotide polymorphism; SLE; SNP
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04142005-161032/, etd-04142005-161032
Date Deposited: 10 Nov 2011 19:37
Last Modified: 15 Nov 2016 13:40
URI: http://d-scholarship.pitt.edu/id/eprint/7146

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