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Epistatic interaction between variations in the angiotensin I converting enzyme and angiotensin II type 1 receptor genes in relation to extent of coronary atherosclerosis

Epistatic interaction between variations in the angiotensin I converting enzyme and angiotensin II type 1 receptor genes in relation to extent of coronary atherosclerosis
Epistatic interaction between variations in the angiotensin I converting enzyme and angiotensin II type 1 receptor genes in relation to extent of coronary atherosclerosis
OBJECTIVE: To test the hypothesis that gene-gene interaction of the renin-angiotensin system is associated with an effect on the extent of coronary atherosclerosis.
SETTING AND RESULTS: A cohort of 1162 patients with coronary artery disease were genotyped for genetic polymorphisms in the renin-angiotensin system. Patients carrying the D allele of the angiotensin I converting enzyme (ACE) gene had greater coronary extent scores (defined as the number of coronary segments with 5% to 75% stenosis) than those not carrying this allele (p = 0.006 in non-parametric analysis and p = 0.019 in parametric analysis). This association remained significant after adjusting for age, body mass index, hypertension, and diabetes, which were also significantly associated with coronary extent scores. There was a significant interaction (p = 0.033) between genotypes of ACE and angiotensin II type 1 receptor (AGTR1). The association between the ACE gene D allele and increased coronary extent scores was significant (p = 0.008 in non-parametric and p = 0.027 in parametric analysis) in those carrying the +1166 C allele of the AGTR1 gene, but was absent in those not carrying the AGTR1 gene +1166 C allele.
CONCLUSION: These findings suggest that variation in the ACE and AGTR1 genes and their interaction may not only contribute to susceptibility of coronary artery disease as previously found but also modify the disease process, thus contributing to interindividual differences in severity of the disease.
epistasis, genetic, renin-angiotensin system, human, genes, angiotensin, patients, methods, diabetes, male, middle aged, gene frequency, type 1, analysis, humans, hypothesis, atherosclerosis, arteries, coronary arteriosclerosis, angiotensin ii, hypertension, female, cohort, disease, research support, peptidyl-dipeptidase a, polymorphism, non-U.S.gov't, genotype, cohort studies, genetics, receptor, receptors, coronary stenosis, polymerase chain reaction, body mass index
1195-1199
Ye, S.
73027825-861c-4bca-8ce6-67a325fa2d2c
Dhillon, S.
ecffb1ad-820f-4191-bcdb-055721e67002
Seear, R.
76ae88ac-eea0-4cb1-a499-ada71a788b30
Dunleavey, L.
4efe3953-6094-4018-a52b-5330141e3167
Day, L.B.
e2afd522-a3f5-4b13-9da9-7f6f6306bc82
Bannister, W.
56615620-e9b3-4b7d-85ce-88abe4e3c29a
Day, I.N.
e9cacaf7-f4c8-4ef0-82fa-b459ad683d50
Simpson, I.
ceb12a1e-d254-43b6-9618-a0ee8087e701
Ye, S.
73027825-861c-4bca-8ce6-67a325fa2d2c
Dhillon, S.
ecffb1ad-820f-4191-bcdb-055721e67002
Seear, R.
76ae88ac-eea0-4cb1-a499-ada71a788b30
Dunleavey, L.
4efe3953-6094-4018-a52b-5330141e3167
Day, L.B.
e2afd522-a3f5-4b13-9da9-7f6f6306bc82
Bannister, W.
56615620-e9b3-4b7d-85ce-88abe4e3c29a
Day, I.N.
e9cacaf7-f4c8-4ef0-82fa-b459ad683d50
Simpson, I.
ceb12a1e-d254-43b6-9618-a0ee8087e701

Ye, S., Dhillon, S., Seear, R., Dunleavey, L., Day, L.B., Bannister, W., Day, I.N. and Simpson, I. (2003) Epistatic interaction between variations in the angiotensin I converting enzyme and angiotensin II type 1 receptor genes in relation to extent of coronary atherosclerosis. Heart, 89 (10), 1195-1199. (doi:10.1136/heart.89.10.1195).

Record type: Article

Abstract

OBJECTIVE: To test the hypothesis that gene-gene interaction of the renin-angiotensin system is associated with an effect on the extent of coronary atherosclerosis.
SETTING AND RESULTS: A cohort of 1162 patients with coronary artery disease were genotyped for genetic polymorphisms in the renin-angiotensin system. Patients carrying the D allele of the angiotensin I converting enzyme (ACE) gene had greater coronary extent scores (defined as the number of coronary segments with 5% to 75% stenosis) than those not carrying this allele (p = 0.006 in non-parametric analysis and p = 0.019 in parametric analysis). This association remained significant after adjusting for age, body mass index, hypertension, and diabetes, which were also significantly associated with coronary extent scores. There was a significant interaction (p = 0.033) between genotypes of ACE and angiotensin II type 1 receptor (AGTR1). The association between the ACE gene D allele and increased coronary extent scores was significant (p = 0.008 in non-parametric and p = 0.027 in parametric analysis) in those carrying the +1166 C allele of the AGTR1 gene, but was absent in those not carrying the AGTR1 gene +1166 C allele.
CONCLUSION: These findings suggest that variation in the ACE and AGTR1 genes and their interaction may not only contribute to susceptibility of coronary artery disease as previously found but also modify the disease process, thus contributing to interindividual differences in severity of the disease.

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More information

Published date: 2003
Keywords: epistasis, genetic, renin-angiotensin system, human, genes, angiotensin, patients, methods, diabetes, male, middle aged, gene frequency, type 1, analysis, humans, hypothesis, atherosclerosis, arteries, coronary arteriosclerosis, angiotensin ii, hypertension, female, cohort, disease, research support, peptidyl-dipeptidase a, polymorphism, non-U.S.gov't, genotype, cohort studies, genetics, receptor, receptors, coronary stenosis, polymerase chain reaction, body mass index

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Local EPrints ID: 60448
URI: http://eprints.soton.ac.uk/id/eprint/60448
PURE UUID: 2927f32f-09b8-4ac7-b806-b0e40520f5d8

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Date deposited: 08 Sep 2008
Last modified: 15 Mar 2024 11:20

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Contributors

Author: S. Ye
Author: S. Dhillon
Author: R. Seear
Author: L. Dunleavey
Author: L.B. Day
Author: W. Bannister
Author: I.N. Day
Author: I. Simpson

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