Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study

Børge G Nordestgaard; Kimmo Kontula; Marianne Benn; Björn Dahlöf; Ulf de Faire; Jonathan M Edelman; Erik Eliasson; Frej Fyhrquist; Darcy A Hille; Hans Ibsen; Paulette A Lyle; Kåre Berg; Mia Sandberg; Amar A Sethi; Peggy H Wong; Ingrid Os; Marianne Benn

doi:10.1097/fpc.0b013e328333f70b

Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study

Børge G Nordestgaard, Kimmo Kontula, Marianne Benn, Björn Dahlöf, Ulf de Faire, Jonathan M Edelman, Erik Eliasson, Frej Fyhrquist, Darcy A Hille, Hans Ibsen, Paulette A Lyle, Kåre Berg, Mia Sandberg, Amar A Sethi, Peggy H Wong, Ingrid Os, Marianne Benn

35 Citations (Scopus)

Abstract

OBJECTIVE: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the β-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol. METHODS: We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol. RESULTS: ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH. CONCLUSION: ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.

Original language	English
Journal	Pharmacogenetics and Genomics
Volume	20
Issue number	2
Pages (from-to)	77-85
Number of pages	8
ISSN	1744-6872
DOIs	https://doi.org/10.1097/fpc.0b013e328333f70b
Publication status	Published - Feb 2010

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Nordestgaard, B. G., Kontula, K., Benn, M., Dahlöf, B., de Faire, U., Edelman, J. M., Eliasson, E., Fyhrquist, F., Hille, D. A., Ibsen, H., Lyle, P. A., Berg, K., Sandberg, M., Sethi, A. A., Wong, P. H., Os, I., & Benn, M. (2010). Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study. Pharmacogenetics and Genomics, 20(2), 77-85. https://doi.org/10.1097/fpc.0b013e328333f70b

Nordestgaard, BG, Kontula, K, Benn, M, Dahlöf, B, de Faire, U, Edelman, JM, Eliasson, E, Fyhrquist, F, Hille, DA, Ibsen, H, Lyle, PA, Berg, K, Sandberg, M, Sethi, AA, Wong, PH, Os, I & Benn, M 2010, 'Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study', Pharmacogenetics and Genomics, vol. 20, no. 2, pp. 77-85. https://doi.org/10.1097/fpc.0b013e328333f70b

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title = "Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study",

abstract = "OBJECTIVE: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the β-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol. METHODS: We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol. RESULTS: ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH. CONCLUSION: ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.",

author = "Nordestgaard, {B{\o}rge G} and Kimmo Kontula and Marianne Benn and Bj{\"o}rn Dahl{\"o}f and {de Faire}, Ulf and Edelman, {Jonathan M} and Erik Eliasson and Frej Fyhrquist and Hille, {Darcy A} and Hans Ibsen and Lyle, {Paulette A} and K{\aa}re Berg and Mia Sandberg and Sethi, {Amar A} and Wong, {Peggy H} and Ingrid Os and Marianne Benn",

year = "2010",

month = feb,

doi = "10.1097/fpc.0b013e328333f70b",

language = "English",

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pages = "77--85",

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TY - JOUR

T1 - Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study

AU - Nordestgaard, Børge G

AU - Kontula, Kimmo

AU - Benn, Marianne

AU - Dahlöf, Björn

AU - de Faire, Ulf

AU - Edelman, Jonathan M

AU - Eliasson, Erik

AU - Fyhrquist, Frej

AU - Hille, Darcy A

AU - Ibsen, Hans

AU - Lyle, Paulette A

AU - Berg, Kåre

AU - Sandberg, Mia

AU - Sethi, Amar A

AU - Wong, Peggy H

AU - Os, Ingrid

AU - Benn, Marianne

PY - 2010/2

Y1 - 2010/2

N2 - OBJECTIVE: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the β-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol. METHODS: We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol. RESULTS: ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH. CONCLUSION: ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.

AB - OBJECTIVE: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the β-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol. METHODS: We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol. RESULTS: ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH. CONCLUSION: ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.

U2 - 10.1097/fpc.0b013e328333f70b

DO - 10.1097/fpc.0b013e328333f70b

M3 - Journal article

SN - 1744-6872

VL - 20

SP - 77

EP - 85

JO - Pharmacogenetics

JF - Pharmacogenetics

IS - 2

ER -

Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study

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