© 1996 American Heart Association, Inc.
Articles |
Polymorphic Markers in Apolipoprotein C-III Gene Flanking Regions and Hypertriglyceridemia
the Department of Medicine, Baylor College of Medicine, Houston, Tex (A.P.S., L.S.); the Human Genetics Center, University of Texas Health Science Center, Houston (G.P.P., E.B.); and the Department of Laboratory Medicine, Landeskrankenanstalten Salzburg, Austria (W.P.).
Correspondence to Eric Boerwinkle, PhD, Human Genetics Center, University of Texas Health Science Center, Houston, TX 77225. E-mail eboerwin@gsbs.gs.uth.tmc.edu.
Abstract
Hypertriglyceridemia and hyperlipidemia are common disorders associated with coronary artery disease and premature death. The proteins encoded by the apolipoprotein (apo) A-I/C-III/A-IV gene cluster are involved in the metabolism of both triglycerides and cholesterol. In a large sample of individuals from the ARIC study, six polymorphic markers were typed and plasma lipid values were measured to determine whether the well-established association between the Sst I S2 allele in the 3'-untranslated region of the apo C-III gene and hypertriglyceridemia was due to disequilibrium with variation in the 5' regulatory region of the apo C-III gene. The Sst I polymorphism was significantly associated with hypertriglyceridemia (P=.006) but not with carotid artery wall thickness, plasma apo C-III levels, or elevated cholesterol. The frequency of the S2 allele was 0.14 in those with high triglyceride levels and 0.05 in those with low triglyceride levels. None of the 5' flanking polymorphisms were significantly associated with any of the plasma lipids studied. There was substantial linkage disequilibrium between the Sst I polymorphism and each of the 5' apo C-III polymorphisms; however, the significant association between the apo C-III haplotypes and hypertriglyceridemia (odds ratio, 4.0; P<.0001) was solely attributable to the effects of the Sst I polymorphism (odds ratio, 3.96). As a part of these analyses, we also defined a unique haplotype that is inversely associated with the occurrence of hypertriglyceridemia, suggesting further molecular analyses of this important gene region.
Key Words: apo C-III • triglycerides • cholesterol • haplotypes • NIDDM
This article has been cited by other articles:
 |
|
 |
|
  J. E. Hokanson, G. L. Kinney, S. Cheng, H. A. Erlich, A. Kretowski, and M. Rewers Susceptibility to Type 1 Diabetes Is Associated With ApoCIII Gene Haplotypes Diabetes, March 1, 2006; 55(3): 834 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Ruiz-Narvaez, Y. Yang, Y. Nakanishi, J. Kirchdorfer, and H. Campos APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica J. Lipid Res., December 1, 2005; 46(12): 2605 - 2613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Cohn, B. W. Patterson, K. D. Uffelman, J. Davignon, and G. Steiner Rate of Production of Plasma and Very-Low-Density Lipoprotein (VLDL) Apolipoprotein C-III Is Strongly Related to the Concentration and Level of Production of VLDL Triglyceride in Male Subjects with Different Body Weights and Levels of Insulin Sensitivity J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3949 - 3955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q.-f. Wang, X. Liu, J. O'Connell, Z. Peng, R. M. Krauss, D. L. Rainwater, J. L. VandeBerg, Edward. M. Rubin, J.-F. Cheng, and L. A. Pennacchio Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons Hum. Mol. Genet., May 15, 2004; 13(10): 1049 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D Tobin, P. S Braund, P. R Burton, J. R Thompson, R. Steeds, K. Channer, S. Cheng, K. Lindpaintner, and N. J Samani Genotypes and haplotypes predisposing to myocardial infarction: a multilocus case-control study Eur. Heart J., March 2, 2004; 25(6): 459 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Olivieri, A. Bassi, C. Stranieri, E. Trabetti, N. Martinelli, F. Pizzolo, D. Girelli, S. Friso, P. F. Pignatti, and R. Corrocher Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease J. Lipid Res., December 1, 2003; 44(12): 2374 - 2381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-T. Kao, H.-C. Wen, K.-L. Chien, H.-C. Hsu, and S.-W. Lin A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia Hum. Mol. Genet., October 1, 2003; 12(19): 2533 - 2539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Aouizerat, M. Kulkarni, D. Heilbron, D. Drown, S. Raskin, C. R. Pullinger, M. J. Malloy, and J. P. Kane Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids J. Lipid Res., June 1, 2003; 44(6): 1167 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Couillard, M.-C. Vohl, J. C. Engert, I. Lemieux, A. Houde, N. Almeras, D. Prud'homme, A. Nadeau, J.-P. Despres, and J. Bergeron Effect of apoC-III gene polymorphisms on the lipoprotein-lipid profile of viscerally obese men J. Lipid Res., May 1, 2003; 44(5): 986 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Pennacchio, M. Olivier, J. A. Hubacek, R. M. Krauss, E. M. Rubin, and J. C. Cohen Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels Hum. Mol. Genet., November 15, 2002; 11(24): 3031 - 3038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Talmud, E. Hawe, S. Martin, M. Olivier, G. J. Miller, E. M. Rubin, L. A. Pennacchio, and S. E. Humphries Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides Hum. Mol. Genet., November 15, 2002; 11(24): 3039 - 3046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Olivieri, C. Stranieri, A. Bassi, B. Zaia, D. Girelli, F. Pizzolo, E. Trabetti, S. Cheng, M. A. Grow, P. F. Pignatti, et al. ApoC-III gene polymorphisms and risk of coronary artery disease J. Lipid Res., September 1, 2002; 43(9): 1450 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Corella, M. Guillen, C. Saiz, O. Portoles, A. Sabater, J. Folch, and J. M. Ordovas Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a Mediterranean population: interaction with tobacco smoking and the APOE locus J. Lipid Res., March 1, 2002; 43(3): 416 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pallaud, R. Gueguen, C. Sass, M. Grow, S. Cheng, G. Siest, and S. Visvikis Genetic influences on lipid metabolism trait variability within the Stanislas Cohort J. Lipid Res., November 1, 2001; 42(11): 1879 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Dallinga-Thie, M. Groenendijk, R. N. H. H. C. Blom, T. W. A. De Bruin, and E. De Kant Genetic heterogeneity in the apolipoprotein C-III promoter and effects of insulin J. Lipid Res., September 1, 2001; 42(9): 1450 - 1456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Talmud, L. Berglund, E. M. Hawe, D. M. Waterworth, C. R. Isasi, R. E. Deckelbaum, T. Starc, H. N. Ginsberg, S. E. Humphries, and S. Shea Age-Related Effects of Genetic Variation on Lipid Levels: The Columbia University BioMarkers Study Pediatrics, September 1, 2001; 108(3): e50 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Groenendijk, R. M. Cantor, T. W. A. De Bruin, and G. M. Dallinga-Thie New genetic variants in the apoA-I and apoC-III genes and familial combined hyperlipidemia J. Lipid Res., February 1, 2001; 42(2): 188 - 194. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. V. Anisimov, M. V. Volkova, L. V. Lenskaya, V. K. Khavinson, D. V. Solovieva, and E. I. Schwartz Age-Associated Accumulation of the Apolipoprotein C-III Gene T-455C Polymorphism C Allele in a Russian Population J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2001; 56(1): 27B - 32. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. M. Waterworth, P. J. Talmud, S. R. Bujac, R. M. Fisher, G. J. Miller, and S. E. Humphries Contribution of Apolipoprotein C-III Gene Variants to Determination of Triglyceride Levels and Interaction With Smoking in Middle-Aged Men Arterioscler. Thromb. Vasc. Biol., December 1, 2000; 20(12): 2663 - 2669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Coon, R. H. Myers, I. B. Borecki, D. K. Arnett, S. C. Hunt, M. A. Province, L. Djousse, and M. F. Leppert Replication of Linkage of Familial Combined Hyperlipidemia to Chromosome 1q With Additional Heterogeneous Effect of Apolipoprotein A-I/C-III/A-IV Locus : The NHLBI Family Heart Study Arterioscler. Thromb. Vasc. Biol., October 1, 2000; 20(10): 2275 - 2280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Waterworth, J. A. Hubacek, J. Pitha, J. Kovar, R. Poledne, S. E. Humphries, and P. J. Talmud Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI;-APOE cluster J. Lipid Res., July 1, 2000; 41(7): 1103 - 1109. [Abstract] [Full Text]
|
|
|
|
|
|
R. Batal, M. Tremblay, P. H. R. Barrett, H. Jacques, A. Fredenrich, O. Mamer, J. Davignon, and J. S. Cohn Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects J. Lipid Res., May 1, 2000; 41(5): 706 - 718. [Abstract] [Full Text]
|
|
|
|
|
|
E. J. G. Sijbrands, M. J. V. Hoffer, A. E. Meinders, L. M. Havekes, R. R. Frants, A. H. M. Smelt, and P. De Knijff Severe Hyperlipidemia in Apolipoprotein E2 Homozygotes Due to a Combined Effect of Hyperinsulinemia and an SstI Polymorphism Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2722 - 2729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Groenendijk, R. M. Cantor, N. H. H. C. Blom, J. I. Rotter, T. W. A. de Bruin, and G. M. Dallinga-Thie Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia J. Lipid Res., June 1, 1999; 40(6): 1036 - 1044. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. M. Waterworth, J. Ribalta, V. Nicaud, J. Dallongeville, S. E. Humphries, and P. Talmud ApoCIII Gene Variants Modulate Postprandial Response to Both Glucose and Fat Tolerance Tests Circulation, April 13, 1999; 99(14): 1872 - 1877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Esterbauer, E. Hell, F. Krempler, and W. Patsch Allele-specific Differences in Apolipoprotein C-III mRNA Expression in Human Liver Clin. Chem., March 1, 1999; 45(3): 331 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Vedie, X. Jeunemaitre, J. L. Megnien, I. Myara, H. Trebeden, A. Simon, and N. Moatti Charge Heterogeneity of LDL in Asymptomatic Hypercholesterolemic Men Is Related to Lipid Parameters and Variations in the ApoB and CIII Genes Arterioscler. Thromb. Vasc. Biol., November 1, 1998; 18(11): 1780 - 1789. [Abstract] [Full Text] [PDF]
|
|