Abstract
Coronary artery disease (CAD) and myocardial infarction (MI) have a genetic basis, but the precise genetic underpinning remains controversial. Recently, an association of the LRP8 R952Q polymorphism (rs5174) with familial premature CAD/MI was reported. We analysed rs5174 (or the perfect proxy rs5177) in 1,210 patients with familial MI and 1,015 controls from the German MI Family study, in 1,926 familial CAD (1,377 with MI) patients and 2,938 controls from the Wellcome Trust Case Control Consortium (WTCCC) MI/CAD cohort, in 346 CAD patients and 351 controls from the AtheroGene study and in 295 men with incident CAD and 301 controls from the Prospective Epidemiological Study of MI study and found no evidence for association in any of the populations studied. In the WTCCC and the German MI Family studies, additional single-nucleotide polymorphisms in the LRP8 gene were analysed and displayed no evidence for association either.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Mayer B, Erdmann J, Schunkert H (2007) Genetics and heritability of coronary artery disease and myocardial infarction. Clin Res Cardiol 96(1):1–7
Fischer M, Broeckel U, Holmer S, Baessler A, Hengstenberg C, Mayer B, Erdmann J, Klein G, Riegger G, Jacob HJ, Schunkert H (2005) Distinct heritable patterns of angiographic coronary artery disease in families with myocardial infarction. Circulation 111(7):855–862
Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357(5):443–453
Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson G, Gudbjartsson DF, Magnusson KP, Andersen K, Levey AI, Backman VM, Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB, Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, Thorgeirsson G, Thorsteinsdottir U, Kong A, Stefansson K (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316(5830):1491–1493
McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC (2007) A common allele on chromosome 9 associated with coronary heart disease. Science 316(5830):1488–1491
Schunkert H, Gotz A, Braund P, McGinnis R, Tregouet DA, Mangino M, Linsel-Nitschke P, Cambien F, Hengstenberg C, Stark K, Blankenberg S, Tiret L, Ducimetiere P, Keniry A, Ghori MJ, Schreiber S, El Mokhtari NE, Hall AS, Dixon RJ, Goodall AH, Liptau H, Pollard H, Schwarz DF, Hothorn LA, Wichmann HE, Konig IR, Fischer M, Meisinger C, Ouwehand W, Deloukas P, Thompson JR, Erdmann J, Ziegler A, Samani NJ (2008) Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease. Circulation 117(13):1675–1684
Wang Q, Rao S, Shen GQ, Li L, Moliterno DJ, Newby LK, Rogers WJ, Cannata R, Zirzow E, Elston RC, Topol EJ (2004) Premature myocardial infarction novel susceptibility locus on chromosome 1P34-36 identified by genomewide linkage analysis. Am J Hum Genet 74(2):262–271
Shen GQ, Li L, Girelli D, Seidelmann SB, Rao S, Fan C, Park JE, Xi Q, Li J, Hu Y, Olivieri O, Marchant K, Barnard J, Corrocher R, Elston R, Cassano J, Henderson S, Hazen SL, Plow EF, Topol EJ, Wang QK (2007) An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction. Am J Hum Genet 81(4):780–791
The Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678
Tiret L, Godefroy T, Lubos E, Nicaud V, Tregouet DA, Barbaux S, Schnabel R, Bickel C, Espinola-Klein C, Poirier O, Perret C, Munzel T, Rupprecht HJ, Lackner K, Cambien F, Blankenberg S (2005) Genetic analysis of the interleukin-18 system highlights the role of the interleukin-18 gene in cardiovascular disease. Circulation 112(5):643–650
Morange PE, Tregouet DA, Frere C, Luc G, Arveiler D, Ferrieres J, Amouyel P, Evans A, Ducimetiere P, Cambien F, Tiret L, Juhan-Vague I (2005) TAFI gene haplotypes, TAFI plasma levels and future risk of coronary heart disease: the PRIME Study. J Thromb Haemost 3(7):1503–1510
Lieb W, Graf J, Gotz A, Konig IR, Mayer B, Fischer M, Stritzke J, Hengstenberg C, Holmer SR, Doring A, Lowel H, Schunkert H, Erdmann J (2006) Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg echocardiographic substudy. J Mol Med 84(1):88–96
Wellek S (2004) Tests for establishing compatibility of an observed genotype distribution with Hardy–Weinberg equilibrium in the case of a biallelic locus. Biometrics 60(3):694–703
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575
Steffens M, Lamina C, Illig T, Bettecken T, Vogler R, Entz P, Suk EK, Toliat MR, Klopp N, Caliebe A, Konig IR, Kohler K, Ludemann J, Diaz LA, Fimmers R, Lichtner P, Ziegler A, Wolf A, Krawczak M, Nurnberg P, Hampe J, Schreiber S, Meitinger T, Wichmann HE, Roeder K, Wienker TF, Baur MP (2006) SNP-based analysis of genetic substructure in the German population. Hum Hered 62(1):20–29
Acknowledgements
This study was supported by the National Genome Network (01GS0418 to Drs. Schunkert, Erdmann and Hengstenberg; 01GR0466 to Drs. Ziegler and König), by the EU sponsored project Cardiogenics (LSH-2006-037593) and by a BMBF grant 010131P3428 of the German Federal Ministry of Education and Research. NJS holds a Chair supported by the British Heart Foundation.
Conflict of interest statement
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
Wolfgang Lieb, Tanja Zeller, Massimo Mangino, Jeanette Erdmann, and Laurence Tiret contributed equally.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Electronic Supplementary Material
(PDF 114 KB)
Rights and permissions
About this article
Cite this article
Lieb, W., Zeller, T., Mangino, M. et al. Lack of association of genetic variants in the LRP8 gene with familial and sporadic myocardial infarction. J Mol Med 86, 1163–1170 (2008). https://doi.org/10.1007/s00109-008-0376-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00109-008-0376-5