IJE Advance Access originally published online on July 15, 2004
International Journal of Epidemiology 2004 33(5):1002-1013; doi:10.1093/ije/dyh275
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IJE vol.33 no.5 © International Epidemiological Association 2004; all rights reserved.
Article |
Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls: discrepancies between genotype, blood lipid concentrations, and coronary disease risk
1 Institute of Human Genetics, University of Newcastle-upon-Tyne, UK
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
6 For information on collaborators and participating centres see end of paper
Correspondence: Bernard Keavney, Institute of Human Genetics, University of Newcastle, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ, UK. 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 
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.
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.
Keywords Genetics, coronary heart disease, lipids
Accepted 2 June 2004
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