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Independent effects of the -219 G>T and ?2/ ?3/ ?4 polymorphisms in the apolipoprotein E gene on coronary artery disease: the Southampton Atherosclerosis Study

Independent effects of the -219 G>T and ?2/ ?3/ ?4 polymorphisms in the apolipoprotein E gene on coronary artery disease: the Southampton Atherosclerosis Study
Independent effects of the -219 G>T and ?2/ ?3/ ?4 polymorphisms in the apolipoprotein E gene on coronary artery disease: the Southampton Atherosclerosis Study
A number of studies have shown that coronary artery disease severity is associated with the ?2/ ?3/ ?4 polymorphism in the coding region of the apolipoprotein E gene. In this study, we investigated whether the severity of the disease was also influenced by a functional polymorphism (-219 G>T) in the promoter of the gene, and if so, whether the effects of the two polymorphisms were independent. A cohort of 1170 patients with angiographically documented coronary artery disease were genotyped for the two polymorphisms. The frequency of the 4 allele of the ?2/ ?3/ ?4 polymorphism increased linearly with increasing number of diseased vessels, so did the -219T allele of the -219 G>T polymorphism. In the sample as a whole, logistic regression analyses indicated that compared with the G/G genotype, the T/T genotype conferred an odds ratio of 1.598 (95% CI=1.161-2.201, P=0.004) in favor of increased disease severity, and the relationship remained significant after adjustment for ?2/? 3/ ?4 polymorphism genotypes, plasma cholesterol and triglyceride levels, and other risk factors. The effect of the T/T genotype on disease severity was more significant in patients who did not carry the 4 allele (OR=1.510, 95% CI=1.028-2.221) than in 4 allele carriers (OR=1.303, 95% CI=0.619-2.742). There was considerable linkage disequilibrium between the two polymorphisms (=0.9, P<0.001). Logistic regression analysis showed that the -219T-4 haplotype conferred an odds ratio of 1.488 (95% CI=1.133-1.954). These findings suggest that the -219 G>T and 2/3/4 polymorphisms, which may affect respectively the quantity and quality of apoE, have independent and possibly additive effects on coronary artery disease severity.
apolipoprotein e, genetic polymorphism, linkage disequilibrium, coronary artery disease
1018-4813
437-443
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab
Dunleavey, Louise
05f074a1-b91e-47d9-98af-84846d68a09b
Bannister, Wendy
d0b81f85-205b-48c9-aa0e-5fe143c7c288
Day, Lorna B.
e2afd522-a3f5-4b13-9da9-7f6f6306bc82
Tapper, William
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Day, Ian N.M.
da3e496f-5262-4595-a20a-6db60aa0bade
Simpson, Iain
a3d9424d-a76f-47c1-9886-7a277e8d7f5f
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab
Dunleavey, Louise
05f074a1-b91e-47d9-98af-84846d68a09b
Bannister, Wendy
d0b81f85-205b-48c9-aa0e-5fe143c7c288
Day, Lorna B.
e2afd522-a3f5-4b13-9da9-7f6f6306bc82
Tapper, William
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Day, Ian N.M.
da3e496f-5262-4595-a20a-6db60aa0bade
Simpson, Iain
a3d9424d-a76f-47c1-9886-7a277e8d7f5f

Ye, Shu, Dunleavey, Louise, Bannister, Wendy, Day, Lorna B., Tapper, William, Collins, Andrew, Day, Ian N.M. and Simpson, Iain (2003) Independent effects of the -219 G>T and ?2/ ?3/ ?4 polymorphisms in the apolipoprotein E gene on coronary artery disease: the Southampton Atherosclerosis Study. European Journal of Human Genetics, 11 (6), 437-443. (doi:10.1038/sj.ejhg.5200983).

Record type: Article

Abstract

A number of studies have shown that coronary artery disease severity is associated with the ?2/ ?3/ ?4 polymorphism in the coding region of the apolipoprotein E gene. In this study, we investigated whether the severity of the disease was also influenced by a functional polymorphism (-219 G>T) in the promoter of the gene, and if so, whether the effects of the two polymorphisms were independent. A cohort of 1170 patients with angiographically documented coronary artery disease were genotyped for the two polymorphisms. The frequency of the 4 allele of the ?2/ ?3/ ?4 polymorphism increased linearly with increasing number of diseased vessels, so did the -219T allele of the -219 G>T polymorphism. In the sample as a whole, logistic regression analyses indicated that compared with the G/G genotype, the T/T genotype conferred an odds ratio of 1.598 (95% CI=1.161-2.201, P=0.004) in favor of increased disease severity, and the relationship remained significant after adjustment for ?2/? 3/ ?4 polymorphism genotypes, plasma cholesterol and triglyceride levels, and other risk factors. The effect of the T/T genotype on disease severity was more significant in patients who did not carry the 4 allele (OR=1.510, 95% CI=1.028-2.221) than in 4 allele carriers (OR=1.303, 95% CI=0.619-2.742). There was considerable linkage disequilibrium between the two polymorphisms (=0.9, P<0.001). Logistic regression analysis showed that the -219T-4 haplotype conferred an odds ratio of 1.488 (95% CI=1.133-1.954). These findings suggest that the -219 G>T and 2/3/4 polymorphisms, which may affect respectively the quantity and quality of apoE, have independent and possibly additive effects on coronary artery disease severity.

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More information

e-pub ahead of print date: 28 May 2003
Published date: 1 June 2003
Additional Information: Copyright © 2003, Nature Publishing Group
Keywords: apolipoprotein e, genetic polymorphism, linkage disequilibrium, coronary artery disease

Identifiers

Local EPrints ID: 25046
URI: http://eprints.soton.ac.uk/id/eprint/25046
ISSN: 1018-4813
PURE UUID: cf8032a5-ba28-45fc-a3f1-29fca9249e7b
ORCID for William Tapper: ORCID iD orcid.org/0000-0002-5896-1889
ORCID for Andrew Collins: ORCID iD orcid.org/0000-0001-7108-0771

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Date deposited: 05 Apr 2006
Last modified: 16 Mar 2024 03:07

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Contributors

Author: Shu Ye
Author: Louise Dunleavey
Author: Wendy Bannister
Author: Lorna B. Day
Author: William Tapper ORCID iD
Author: Andrew Collins ORCID iD
Author: Ian N.M. Day
Author: Iain Simpson

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