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Association of Hepatic Lipase and Endothelial Lipase Polymorphisms with Variation in NMR Lipoprotein Subclasses in Caucasian, African-American and African-Caribbean older Men

Miljkovic-Gacic, Iva (2004) Association of Hepatic Lipase and Endothelial Lipase Polymorphisms with Variation in NMR Lipoprotein Subclasses in Caucasian, African-American and African-Caribbean older Men. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Despite higher prevalence of risk factors for coronary heart disease, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than Caucasians. In part, this is thought to be due to the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower levels of triglycerides and higher levels of HDL-C. The aim of the present study was to investigate the genetic contribution of two candidate genes, endothelial lipase (LIPG) and hepatic lipase (LIPC), to the ethnic variation in nuclear magnetic resonance (NMR) measured lipoproteins in 600 Caucasian, 100 African-American and 205 Tobago African-Caribbean men, older than 65 years. First, using a set of six ancestry informative markers, we estimated high African genetic contribution in the Tobago population (94%). A more favorable lipoprotein profile was observed in men of African origin compared to Caucasians. The frequency of the LIPG 584T allele in Tobago men (0.06) was five times less common than in Caucasians (0.29) and two times less common than in African-Americans (0.14). In African-Caribbeans, 584T allele was associated with lower small HDL and a greater HDL size, whereas in Caucasians and African-Americans, no significant association was found. Although, the LIPG 584T allele is protective in African-Caribbean men, its frequency is too low to explain the more favorable lipoprotein profile observed in these men. In contrast, the frequency of the LIPC -514T allele (0.57) was somewhat higher than the frequency in African-Americans (0.49), and three times as high as the frequency in Caucasians (0.20). 514C>T interacted with ethnicity to affect the levels of HDL-C, large HDL and HDL and LDL size. Carriers of 514T allele in both populations of African origin, but not in Caucasians, had elevated large HDL and greater HDL size. The higher frequency of the LIPC -514T allele in men of African origin significantly contributes to the more favorable distribution of HDL subclasses compared with Caucasians. Our findings have important public health relevance as they increase our understanding of Black-White differences in lipoprotein distributions, and are likely to increase our understanding of the underlying causes behind the ethnic differences in susceptibility to atherosclerosis.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Miljkovic-Gacic, Ivaivm1@pitt.edu, ivami@yahoo.comIVM1
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBunker, Clareann Hbunkerc@pitt.eduBUNKERC
Committee MemberKammerer, Candace Mcandace.kammerer@hgen.pitt.eduCMK3
Committee MemberKuller, Lewis HKullerL@edc.pitt.eduKULLER
Committee MemberEvans, Rhobert WEvansR@edc.pitt.eduRWE2
Committee MemberFerrell, Robert Erferrell@hgen.pitt.eduRFERRELL
Date: 15 December 2004
Date Type: Completion
Defense Date: 6 December 2004
Approval Date: 15 December 2004
Submission Date: 10 December 2004
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: African-American; Ethnicity; Hepatic lipase; Lipoproteins; NMR; African-Caribbean; Caucasian; Endothelial lipase
Other ID: http://etd.library.pitt.edu/ETD/available/etd-12102004-160222/, etd-12102004-160222
Date Deposited: 10 Nov 2011 20:10
Last Modified: 15 Nov 2016 13:54
URI: http://d-scholarship.pitt.edu/id/eprint/10279

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