IJE Advance Access published online on July 15, 2004
International Journal of Epidemiology, doi:10.1093/ije/dyh275
© 2004 by International Epidemiological Association
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Institute of Human Genetics, University of Newcastle-upon-Tyne, UK
* To whom correspondence should be addressed. E-mail: b.d.keavney{at}ncl.ac.uk.
Background Blood lipid concentrations are causally related to the risk of coronary heart disease (CHD). Various associations between CHD risk and genes that moderately affect plasma lipid levels have been described, but previous studies have typically involved too few ‘cases’ to assess these associations reliably. Methods The present study involves 4685 cases of myocardial infarction (MI) and 3460 unrelated controls without diagnosed cardiovascular disease. Six polymorphisms of four ‘lipid-related’ genes were genotyped. Results For the apolipoprotein E Conclusions It remains unresolved why some of these genetic factors that produce lifelong effects on plasma lipid concentrations have significantly less than the correspondingly expected effects on CHD rates in adult life.
Original paper
Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls: discrepancies between genotype, blood lipid concentrations, and coronary disease risk
2 Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, University of Oxford, UK
3 Department of Public Health, University of Cambridge, UK
4 Tropical Metabolism Research Unit, University of the West Indies, Kingston, Jamaica
5 Centre National de Genotypage, Paris
Abstract 
2/3/4 polymorphism, the average increase in the plasma ratio of apolipoprotein B to apolipoprotein A1 (apoB/apoA1 ratio) among controls was 0.082 (s.e. 0.007) per stepwise change from 3/2 to 3/3 to 3/4 genotype (trend P < 0.0001). The case-control comparison yielded a risk ratio for MI of 1.16 (95% CI: 1.06, 1.27; P = 0.001) per stepwise change in these genotypes. But, this risk ratio was not as extreme as would have been expected from the corresponding differences in plasma apoB/apoA1 ratio between genotypes. Hence, following adjustment for the measured level of the plasma apoB/apoA1 ratio, the direction of the risk ratio per stepwise change reversed to 0.83 (95% CI: 0.74, 0.92; P < 0.001). Similarly, for the apolipoprotein B Asn4311Ser and Thr71Ile polymorphisms, genotypes associated with more adverse plasma apolipoprotein concentrations were associated with significantly lower risk of MI after adjustment for the apoB/apoA1 ratio. The B2 allele of the Cholesteryl ester transfer protein TaqIb polymorphism was associated with a significantly lower plasma apoB/apoA1 ratio, but with no significant difference in the risk of MI. Finally, the lipoprotein lipase, Asn291Ser and T4509C (PvuII) polymorphisms did not produce clear effects on either the plasma apoB/apoA1 ratio or the risk of MI.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Ward, P. N. Mitrou, R. Bowman, R. Luben, N. J. Wareham, K.-T. Khaw, and S. Bingham APOE Genotype, Lipids, and Coronary Heart Disease Risk: A Prospective Population Study Arch Intern Med, August 10, 2009; 169(15): 1424 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Anand, C. Xie, G. Pare, A. Montpetit, S. Rangarajan, M. J. McQueen, H. J. Cordell, B. Keavney, S. Yusuf, T. J. Hudson, et al. Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups: The INTERHEART Genetics Study Circ Cardiovasc Genet, February 1, 2009; 2(1): 16 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ridker, G. Pare, A. N. Parker, R. Y.L. Zee, J. P. Miletich, and D. I. Chasman Polymorphism in the CETP Gene Region, HDL Cholesterol, and Risk of Future Myocardial Infarction: Genomewide Analysis Among 18 245 Initially Healthy Women From the Women's Genome Health Study Circ Cardiovasc Genet, February 1, 2009; 2(1): 26 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Grammer, W. Marz, W. Renner, B. O. Bohm, and M. M. Hoffmann C-reactive protein genotypes associated with circulating C-reactive protein but not with angiographic coronary artery disease: the LURIC study Eur. Heart J., January 2, 2009; 30(2): 170 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 A. Thompson, E. Di Angelantonio, N. Sarwar, S. Erqou, D. Saleheen, R. P. F. Dullaart, B. Keavney, Z. Ye, and J. Danesh Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk JAMA, June 18, 2008; 299(23): 2777 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Benn, M. C. A. Stene, B. G. Nordestgaard, G. B. Jensen, R. Steffensen, and A. Tybjaerg-Hansen Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of Low-Density Lipoprotein Cholesterol in the General Population J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 1038 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Bennet, E. Di Angelantonio, Z. Ye, F. Wensley, A. Dahlin, A. Ahlbom, B. Keavney, R. Collins, B. Wiman, U. de Faire, et al. Association of Apolipoprotein E Genotypes With Lipid Levels and Coronary Risk JAMA, September 19, 2007; 298(11): 1300 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Didelez and N. Sheehan Mendelian randomization as an instrumental variable approach to causal inference Statistical Methods in Medical Research, August 1, 2007; 16(4): 309 - 330. [Abstract] [PDF]
|
|
|
|
|
|
B. Keavney Toll the bell for another genetic association? Eur. Heart J., November 1, 2006; 27(21): 2489 - 2490. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Keavney, J. Danesh, S. Parish, A. Palmer, S. Clark, L. Youngman, M. Delepine, M. Lathrop, R. Peto, R. Collins, et al. Fibrinogen and coronary heart disease: test of causality by 'Mendelian randomization' Int. J. Epidemiol., August 1, 2006; 35(4): 935 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Smith Randomised by (your) god: robust inference from an observational study design J Epidemiol Community Health, May 1, 2006; 60(5): 382 - 388. [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Kolovou, K. K. Anagnostopoulou, K. D. Salpea, D. B. Panagiotakos, I. S. Hoursalas, M. A. Cariolou, K. Koniavitou, and D. V. Cokkinos Apolipoprotein E Genotype in Matched Men and Women with Coronary Heart Disease Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 391 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Davey Smith Genetic epidemiology: an 'enlightened narrative'? Int. J. Epidemiol., October 1, 2004; 33(5): 923 - 924. [Full Text] [PDF]
|
|
|
|
|
|
L. J Palmer The New Epidemiology: putting the pieces together in complex disease aetiology Int. J. Epidemiol., October 1, 2004; 33(5): 925 - 928. [Full Text] [PDF]
|
|