Advertisement

Association of endothelial lipase gene (LIPG) haplotypes with high-density lipoprotein cholesterol subfractions and apolipoprotein AI plasma levels in Japanese Americans

      Abstract

      The LIPG gene on chromosome 18 encodes for endothelial lipase, a member of the triglyceride lipase family. Mouse models suggest that variation in LIPG influences high-density lipoprotein (HDL) metabolism, but only limited data are available in humans. This study examined associations of LIPG haplotypes, comprising a single nucleotide polymorphism (SNP) in the promoter region (−384A > C), and a nonsynonymous SNP in exon 3 (Thr111Ile or 584C > T), with lipoprotein risk factors in 541 adult Japanese Americans. A marginal association was found between LIPG diplotypes and HDL cholesterol (p = 0.045). Stronger associations were seen for HDL3 cholesterol (p = 0.005) and Apolipoprotein AI plasma levels (p = 0.002). After adjustment for age, gender, smoking and medications, individuals homozygous for the minor allele at both SNPs (*4 haplotype) had a more favorable risk factor profile, compared to other haplotype combinations. No relationship was seen for plasma triglyceride levels or low-density lipoprotein (LDL) size, but the homozygous *4 diplotype was also associated with lower Apolipoprotein B and LDL cholesterol levels (p = 0.001 and 0.015, respectively). In conclusion, this community-based family study of Japanese Americans demonstrates that LIPG variants are associated with HDL related risk factors, and may play a role in susceptibility to cardiovascular disease in this population.

      Abbreviations:

      SNP (single nucleotide polymorphism), C (cholesterol), EL (endothelial lipase), HDL (high-density lipoprotein), HL (hepatic lipase), LDL (low-density lipoprotein), LPL (lipoprotein lipase)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Gordon D.J.
        • Rifkind B.M.
        High-density lipoprotein – the clinical implications of recent studies.
        N Engl J Med. 1989; 321: 1311-1316
        • Castelli W.P.
        • Anderson K.
        • Wilson P.W.
        • Levy D.
        Lipids and risk of coronary heart disease. The Framingham Study.
        Ann Epidemiol. 1992; 2: 23-28
        • Rubins H.B.
        • Robins S.J.
        • Collins D.
        • et al.
        Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.
        N Engl J Med. 1999; 341: 410-418
        • Heller D.A.
        • de Faire U.
        • Pedersen N.L.
        • Dahlen G.
        • McClearn G.E.
        Genetic and environmental influences on serum lipid levels in twins.
        N Engl J Med. 1993; 328: 1150-1156
        • Austin M.A.
        • King M.C.
        • Bawol R.D.
        • Hulley S.B.
        • Friedman G.D.
        Risk factors for coronary heart disease in adult female twins. Genetic heritability and shared environmental influences.
        Am J Epidemiol. 1987; 125: 308-318
        • Stampfer M.J.
        • Sacks F.M.
        • Salvini S.
        • Willett W.C.
        • Hennekens C.H.
        A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.
        N Engl J Med. 1991; 325: 373-381
        • Sweetnam P.M.
        • Bolton C.H.
        • Yarnell J.W.
        • et al.
        Associations of the HDL2 and HDL3 cholesterol subfractions with the development of ischemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies.
        Circulation. 1994; 90: 769-774
        • Morgan J.
        • Carey C.
        • Lincoff A.
        • Capuzzi D.
        High-density lipoprotein subfractions and risk of coronary artery disease.
        Curr Atheroscler Rep. 2004; 6: 359-365
        • Jaye M.
        • Lynch K.J.
        • Krawiec J.
        • et al.
        A novel endothelial-derived lipase that modulates HDL metabolism.
        Nat Genet. 1999; 21: 424-428
        • Hirata K.
        • Dichek H.L.
        • Cioffi J.A.
        • et al.
        Cloning of a unique lipase from endothelial cells extends the lipase gene family.
        J Biol Chem. 1999; 274: 14170-14175
        • Jin W.
        • Marchadier D.
        • Rader D.J.
        Lipases and HDL metabolism.
        Trends Endocrinol Metab. 2002; 13: 174-178
        • Broedl U.C.
        • Jin W.
        • Rader D.J.
        Endothelial lipase: a modulator of lipoprotein metabolism upregulated by inflammation.
        Trends Cardiovasc Med. 2004; 14: 202-206
        • Ishida T.
        • Choi S.
        • Kundu R.K.
        • et al.
        Endothelial lipase is a major determinant of HDL level.
        J Clin Invest. 2003; 111: 347-355
        • Jin W.
        • Millar J.S.
        • Broedl U.
        • Glick J.M.
        • Rader D.J.
        Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo.
        J Clin Invest. 2003; 111: 357-362
        • Broedl U.C.
        • Maugeais C.
        • Millar J.S.
        • et al.
        Endothelial lipase promotes the catabolism of Apo B-containing lipoproteins.
        Circ Res. 2004; 94: 1554-1561
        • Ma K.
        • Cilingiroglu M.
        • Otvos J.D.
        • et al.
        Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism.
        Proc Natl Acad Sci USA. 2003; 100: 2748-2753
        • Mank-Seymour A.R.
        • Durham K.L.
        • Thompson J.F.
        • Seymour A.B.
        • Milos P.M.
        Association between single-nucleotide polymorphisms in the endothelial lipase (LIPG) gene and high-density lipoprotein cholesterol levels.
        Biochim Biophys Acta. 2004; 1636: 40-46
        • deLemos A.S.
        • Wolfe M.L.
        • Long C.J.
        • Sivapackianathan R.
        • Rader D.J.
        Identification of genetic variants in endothelial lipase in persons with elevated high-density lipoprotein cholesterol.
        Circulation. 2002; 106: 1321-1326
        • Yamakawa-Kobayashi K.
        • Yanagi H.
        • Endo K.
        • Arinami T.
        • Hamaguchi H.
        Relationship between serum HDL-C levels and common genetic variants of the endothelial lipase gene in Japanese school-aged children.
        Hum Genet. 2003; 113: 311-315
        • Zondervan K.T.
        • Cardon L.R.
        The complex interplay among factors that influence allelic association.
        Nat Rev Genet. 2004; 5: 89-100
        • Austin M.A.
        • Talmud P.J.
        • Farin F.M.
        • et al.
        Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans.
        Biochim Biophys Acta. 2004; 1688: 1-9
        • Fujimoto W.Y.
        • Leonetti D.L.
        • Kinyoun J.L.
        • et al.
        Prevalence of diabetes mellitus and impaired glucose tolerance among second-generation Japanese–American men.
        Diabetes. 1987; 36: 721-729
        • Tsunehara C.H.
        • Leonetti D.L.
        • Fujimoto W.Y.
        Diet of second-generation Japanese–American men with and without non-insulin-dependent diabetes.
        Am J Clin Nutr. 1990; 52: 731-738
        • Warnick G.R.
        • Benderson J.
        • Albers J.J.
        Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol.
        Clin Chem. 1982; 28: 1379-1388
        • Bachorik P.S.
        • Albers J.J.
        Precipitation methods for quantification of lipoproteins.
        Meth Enzymol. 1986; 129: 78-100
        • Carlson C.S.
        • Eberle M.A.
        • Rieder M.J.
        • et al.
        Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium.
        Am J Hum Genet. 2004; 74: 106-120
        • Abecasis G.R.
        • Cardon L.R.
        • Cookson W.O.
        A general test of association for quantitative traits in nuclear families.
        Am J Hum Genet. 2000; 66: 279-292
        • Halverstadt A.
        • Phares D.A.
        • Ferrell R.E.
        • et al.
        High-density lipoprotein–cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype.
        Metabolism. 2003; 52: 1505-1511
        • Paradis M.E.
        • Couture P.
        • Bosse Y.
        • et al.
        The T111I mutation in the EL gene modulates the impact of dietary fat on the HDL profile in women.
        J Lipid Res. 2003; 44: 1902-1908
        • Schaid D.J.
        • Jacobsen S.J.
        Biased tests of association: comparisons of allele frequencies when departing from Hardy–Weinberg proportions.
        Am J Epidemiol. 1999; 149: 706-711