Carr Molly C, Brunzell John D, Deeb Samir S
Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA.
J Lipid Res. 2004 Mar;45(3):466-73. doi: 10.1194/jlr.M300295-JLR200. Epub 2003 Dec 1.
Hepatic lipase activity (HLA) is a determinant of HDL levels, and a polymorphism in the hepatic lipase gene (LIPC) promoter (C-514T) has been hypothesized to account for higher HDL in blacks and Japanese compared with whites. To determine whether the polymorphism contributes to ethnic differences in HDL, we compared LIPC allele frequencies and HLA in Japanese American (JA; n = 84), black American (BA; n = 94), and white American (WA; n = 110) men and women. The LIPC polymorphism was associated with HLA in all cohorts (BA, P = 0.012; JA, P = 0.008; WA, P = 0.009). WA men had 49% and 58% higher HLA than BA and JA men, respectively (both P < 0.05), yet no differences in HLA were found between the women. The higher HLA in the WA men remained after adjustment for the LIPC polymorphism's effect on HLA (P = 0.037) but was erased after adjustment for waist-to-hip-ratio (P = 0.46). Although the WA men had lower HDL and HDL(3) than the JA and BA men (all P < 0.05), there were no differences in HDL(2), implying that variance in HLA may not underlie the ethnic differences in HDL levels. These results suggest that 1) the LIPC promoter polymorphism contributes to variation in HLA and HDL(2) in the three ethnic groups; 2) WA men had higher HLA than BA and JA men, related to ethnic differences in central adiposity but not LIPC allele frequency; and 3) the higher HLA in WA men did not contribute to the ethnic differences in HDL, as the differences in HDL were made up entirely of differences in HDL(3) and not HDL(2).
肝脂肪酶活性（HLA）是高密度脂蛋白（HDL）水平的一个决定因素，并且有人推测肝脂肪酶基因（LIPC）启动子中的一种多态性（C-514T）可解释与白人相比黑人和日本人中较高的HDL水平。为了确定这种多态性是否导致HDL的种族差异，我们比较了日裔美国人（JA；n = 84）、非裔美国人（BA；n = 94）和白人美国人（WA；n = 110）男性和女性的LIPC等位基因频率和HLA。在所有队列中，LIPC多态性均与HLA相关（BA，P = 0.012；JA，P = 0.008；WA，P = 0.009）。WA男性的HLA分别比BA和JA男性高49%和58%（均P < 0.05），但女性之间未发现HLA差异。在调整LIPC多态性对HLA的影响后，WA男性较高的HLA仍然存在（P = 0.037），但在调整腰臀比后消失（P = 0.46）。尽管WA男性的HDL和HDL(3)低于JA和BA男性（均P < 0.05），但HDL(2)没有差异，这意味着HLA的差异可能不是HDL水平种族差异的基础。这些结果表明：1）LIPC启动子多态性导致了这三个种族群体中HLA和HDL(2)的变异；2）WA男性的HLA高于BA和JA男性，这与中心性肥胖的种族差异有关，而与LIPC等位基因频率无关；3）WA男性较高的HLA并未导致HDL的种族差异，因为HDL的差异完全由HDL(3)的差异构成，而非HDL(2)。
