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