Arteriosclerosis and Thrombosis, Vol 14, 1090-1097, Copyright © 1994 by American Heart Association

ARTICLES

DNA variants at the LPL gene locus associate with angiographically defined severity of atherosclerosis and serum lipoprotein levels in a Welsh population

RK Mattu, EW Needham, R Morgan, A Rees, AK Hackshaw, J Stocks, PC Elwood and DJ Galton
Department of Human Genetics and Metabolism, St. Bartholomew's Hospital Medical College, London, UK.

Coronary artery disease (CAD) patients (n = 235), comprising minimal (CAD-, n = 124) and severe (CAD+, n = 111) CAD, were recruited on the basis of their angiographic scores. Male control subjects (n = 123) were selected randomly from the Caerphilly Heart Study cohort. Subjects were genotyped for the Ser447-Ter mutation and HindIII/Pvu II restriction fragment length polymorphisms of the lipoprotein lipase gene and investigated for associations with severity and development of CAD and lipid and lipoprotein levels. The Ser447-Ter mutation showed no significant associations with CAD or dyslipidemia but was related to favorable lipid and lipoprotein profiles. The H2H2 genotype (P < .05) and H2 allele (P = .05) were significantly more frequent in CAD+ versus CAD- and control subjects versus CAD-. H2H2 subjects, among the entire male cohort, had significantly higher levels of apolipoprotein B (P = .0002), total cholesterol (P < .004), and triglycerides (P < .04) than alternative genotypes. P2P2 associated with significantly lower high- density lipoprotein cholesterol levels (P < .01). The H2 allele had most significant associations with raised apolipoprotein B levels compared with other biochemical parameters. Our data suggest that the H2 allele may be a linkage marker for an etiologic mutation for dyslipidemia and the severity and development of atherosclerosis; this is not the Ser447-Ter mutation.

This article has been cited by other articles:

				G. S. Sagoo, I. Tatt, G. Salanti, A. S. Butterworth, N. Sarwar, M. van Maarle, J. W. Jukema, B. Wiman, J. J. P. Kastelein, A. M. Bennet, et al. Seven Lipoprotein Lipase Gene Polymorphisms, Lipid Fractions, and Coronary Disease: A HuGE Association Review and Meta-Analysis Am. J. Epidemiol., December 1, 2008; 168(11): 1233 - 1246. [Abstract] [Full Text] [PDF]

				J. Rip, M. C. Nierman, C. J. Ross, J. W. Jukema, M. R. Hayden, J. J.P. Kastelein, E. S.G. Stroes, and J. A. Kuivenhoven Lipoprotein Lipase S447X: A Naturally Occurring Gain-of-Function Mutation Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1236 - 1245. [Abstract] [Full Text] [PDF]

				R. A. Hegele, C. J.D. Ross, J. Twisk, J. A. Kuivenhoven, J. Rip, J. J. Kastelein, and M. R. Hayden Gene therapy with lipoprotein lipase variant S447X. Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): e25 - e25. [Full Text] [PDF]

				C. J.D. Ross, G. Liu, J. A. Kuivenhoven, J. Twisk, J. Rip, W. van Dop, K. J.D. Ashbourne Excoffon, S. M.E. Lewis, J. J. Kastelein, and M. R. Hayden Complete Rescue of Lipoprotein Lipase-Deficient Mice by Somatic Gene Transfer of the Naturally Occurring LPLS447X Beneficial Mutation Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2143 - 2150. [Abstract] [Full Text] [PDF]

				P. S. Monraats, J. S. Rana, M. C. Nierman, N. M.M. Pires, A. H. Zwinderman, J. J.P. Kastelein, J. A. Kuivenhoven, M. P.M. de Maat, S. Z.H. Rittersma, A. Schepers, et al. Lipoprotein Lipase Gene Polymorphisms and the Risk of Target Vessel Revascularization After Percutaneous Coronary Intervention J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1093 - 1100. [Abstract] [Full Text] [PDF]

				M. O. Goodarzi, H. Wong, M. J. Quinones, K. D. Taylor, X. Guo, L. W. Castellani, H. J. Antoine, H. Yang, W. A. Hsueh, and J. I. Rotter The 3' Untranslated Region of the Lipoprotein Lipase Gene: Haplotype Structure and Association with Post-Heparin Plasma Lipase Activity J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4816 - 4823. [Abstract] [Full Text] [PDF]

				M. E. Brousseau, A. L. Goldkamp, D. Collins, S. Demissie, A. C. Connolly, L. A. Cupples, J. M. Ordovas, H. E. Bloomfield, S. J. Robins, and E. J. Schaefer Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease: The Veterans Affairs HDL Intervention Trial J. Lipid Res., October 1, 2004; 45(10): 1885 - 1891. [Abstract] [Full Text] [PDF]

				J. Lopez-Miranda, G. Cruz, P. Gomez, C. MarIn, E. Paz, P. Perez-MartInez, F. J. Fuentes, J. M. Ordovas, and F. Perez-Jimenez The Influence of Lipoprotein Lipase Gene Variation on Postprandial Lipoprotein Metabolism J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4721 - 4728. [Abstract] [Full Text] [PDF]

				M. O. Goodarzi, X. Guo, K. D. Taylor, M. J. Quinones, M. F. Saad, H. Yang, W. A. Hsueh, and J. I. Rotter Lipoprotein Lipase Is a Gene for Insulin Resistance in Mexican Americans Diabetes, January 1, 2004; 53(1): 214 - 220. [Abstract] [Full Text] [PDF]

				J. D. Spence, M. R. Ban, and R. A. Hegele Lipoprotein Lipase (LPL) Gene Variation and Progression of Carotid Artery Plaque Stroke, May 1, 2003; 34(5): 1176 - 1180. [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]

				Y. Shimo-Nakanishi, T. Urabe, N. Hattori, Y. Watanabe, T. Nagao, M. Yokochi, M. Hamamoto, and Y. Mizuno Polymorphism of the Lipoprotein Lipase Gene and Risk of Atherothrombotic Cerebral Infarction in the Japanese Stroke, July 1, 2001; 32(7): 1481 - 1486. [Abstract] [Full Text] [PDF]

				S. R Holmer, C. Hengstenberg, B. Mayer, A. Doring, H. Lowel, S. Engel, H.-W. Hense, M. Wolf, G. Klein, G. A.J Riegger, et al. Lipoprotein lipase gene polymorphism, cholesterol subfractions and myocardial infarction in large samples of the general population Cardiovasc Res, September 1, 2000; 47(4): 806 - 812. [Abstract] [Full Text] [PDF]

				S. M. Clee, N. Bissada, F. Miao, L. Miao, A. D. Marais, H. E. Henderson, P. Steures, J. McManus, B. McManus, R. C. LeBoeuf, et al. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis J. Lipid Res., April 1, 2000; 41(4): 521 - 531. [Abstract] [Full Text]

				I. Larson, M. M. Hoffmann, J. M. Ordovas, E. J. Schaefer, W. Marz, and J. Kreuzer The Lipoprotein Lipase HindIII Polymorphism: Association with Total Cholesterol and LDL-Cholesterol, but not with HDL and Triglycerides in 342 Females Clin. Chem., July 1, 1999; 45(7): 963 - 968. [Abstract] [Full Text] [PDF]

				H. H. Wittrup, A. Tybjærg-Hansen, and B. G. Nordestgaard Lipoprotein Lipase Mutations, Plasma Lipids and Lipoproteins, and Risk of Ischemic Heart Disease : A Meta-Analysis Circulation, June 8, 1999; 99(22): 2901 - 2907. [Abstract] [Full Text] [PDF]

				D.J. Galton and G.A.A. Ferns Genetic markers to predict polygenic disease: a new problem for social genetics QJM, April 1, 1999; 92(4): 223 - 232. [Abstract] [Full Text] [PDF]

				J. L. Anderson, G. J. King, T. L. Bair, S. P. Elmer, J. B. Muhlestein, J. Habashi, L. Mixson, and J. F. Carlquist Association of lipoprotein lipase gene polymorphisms with coronary artery disease J. Am. Coll. Cardiol., March 15, 1999; 33(4): 1013 - 1020. [Abstract] [Full Text] [PDF]

				P. J. Talmud, S. Hall, S. Holleran, R. Ramakrishnan, H. N. Ginsberg, and S. E. Humphries LPL promoter -93T/G transition influences fasting and postprandial plasma triglycerides response in African-Americans and Hispanics J. Lipid Res., June 1, 1998; 39(6): 1189 - 1196. [Abstract] [Full Text]

				S. E. Humphries, V. Nicaud, J. Margalef, L. Tiret, P. J. Talmud, and f. t. EARS Lipoprotein Lipase Gene Variation Is Associated With a Paternal History of Premature Coronary Artery Disease and Fasting and Postprandial Plasma Triglycerides : The European Atherosclerosis Research Study (EARS) Arterioscler Thromb Vasc Biol, April 1, 1998; 18(4): 526 - 534. [Abstract] [Full Text] [PDF]

				J. A. Thorn, E. W. A. Needham, R. K. Mattu, J. Stocks, and D. J. Galton The Ser447–Ter mutation of the lipoprotein lipase gene relates to variability of serum lipid and lipoprotein levels in monozygotic twins1 J. Lipid Res., February 1, 1998; 39(2): 437 - 441. [Abstract] [Full Text]

				L. Perusse, T. Rice, J. P. Despres, J. Bergeron, M. A. Province, J. Gagnon, A. S. Leon, D. C. Rao, J. S. Skinner, J. H. Wilmore, et al. Familial Resemblance of Plasma Lipids, Lipoproteins and Postheparin Lipoprotein and Hepatic Lipases in the HERITAGE Family Study Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3263 - 3269. [Abstract] [Full Text]

				H. Knoblauch, A. Busjahn, S. Munter, Z. Nagy, H.-D. Faulhaber, H. Schuster, and F. C. Luft Heritability Analysis of Lipids and Three Gene Loci in Twins Link the Macrophage Scavenger Receptor to HDL Cholesterol Concentrations Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2054 - 2060. [Abstract] [Full Text]

				S. Salinelli, J.-Y. Lo, M. P. Mims, E. Zsigmond, L. C. Smith, and L. Chan Structure-Function Relationship of Lipoprotein Lipase-mediated Enhancement of Very Low Density Lipoprotein Binding and Catabolism by the Low Density Lipoprotein Receptor. FUNCTIONAL IMPORTANCE OF A PROPERLY FOLDED SURFACE LOOP COVERING THE CATALYTIC CENTER J. Biol. Chem., September 6, 1996; 271(36): 21906 - 21913. [Abstract] [Full Text] [PDF]

				X.L. Wang, R.M. McCredie, and D.E.L. Wilcken Common DNA Polymorphisms at the Lipoprotein Lipase Gene : Association With Severity of Coronary Artery Disease and Diabetes Circulation, April 1, 1996; 93(7): 1339 - 1345. [Abstract] [Full Text]

				C. Gerdes, L. U. Gerdes, P. S. Hansen, and O. Faergeman Polymorphisms in the Lipoprotein Lipase Gene and Their Associations With Plasma Lipid Concentrations in 40-Year-Old Danish Men Circulation, October 1, 1995; 92(7): 1765 - 1769. [Abstract] [Full Text]

				M.-C. Vohl, B. Lamarche, S. Moorjani, D. Prud'homme, A. Nadeau, C. Bouchard, P.-J. Lupien, and J.-P. Despres The Lipoprotein Lipase HindIII Polymorphism Modulates Plasma Triglyceride Levels in Visceral Obesity Arterioscler Thromb Vasc Biol, May 1, 1995; 15(5): 714 - 720. [Abstract] [Full Text]