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Kurland, Lisa
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Publications (5 of 5) Show all publications
Liljedahl, U., Lind, L., Kurland, L., Berglund, L., Kahan, T. & Syvänen, A.-C. (2004). Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment. BMC Cardiovascular Disorders, 4(1), 16
Open this publication in new window or tab >>Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment
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2004 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 4, no 1, p. 16-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment. METHODS: Ten single nucleotide polymorphisms (SNP) in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the beta1-adrenergic receptor blocker atenolol for twelve weeks. RESULTS: The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele. CONCLUSIONS: Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.

Keywords
Antihypertensive treatment, pharmacogenetics, lipids, minisequencing, genotyping
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-73315 (URN)10.1186/1471-2261-4-16 (DOI)15453913 (PubMedID)
Available from: 2005-06-02 Created: 2005-06-02 Last updated: 2017-12-14Bibliographically approved
Kurland, L. (2003). The antihypertensive response to irbesartan treatment from a pharmacogenetic perspective.. Minerva Med, 94(4), 251-8
Open this publication in new window or tab >>The antihypertensive response to irbesartan treatment from a pharmacogenetic perspective.
2003 (English)In: Minerva Med, ISSN 0026-4806, Vol. 94, no 4, p. 251-8Article in journal (Refereed) Published
Keywords
Antihypertensive Agents/*therapeutic use, Biphenyl Compounds/*therapeutic use, Cytochrome P-450 CYP2D6/genetics, Humans, Hypertension/*drug therapy/genetics, Pharmacogenetics, Pharmacokinetics, Polymorphism; Genetic, Renin-Angiotensin System/genetics, Tetrazoles/*therapeutic use
Identifiers
urn:nbn:se:uu:diva-73405 (URN)14605589 (PubMedID)
Available from: 2005-06-03 Created: 2005-06-03 Last updated: 2011-01-13
Kurland, L., Melhus, H., Karlsson, J., Kahan, T., Malmqvist, K., Öhman, P., . . . Lind, L. (2002). Aldosterone synthase (CYP11B2) -344 C/T polymorphism is related to antihypertensive response: result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. American Journal of Hypertension, 15(5), 389-93
Open this publication in new window or tab >>Aldosterone synthase (CYP11B2) -344 C/T polymorphism is related to antihypertensive response: result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial
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2002 (English)In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 15, no 5, p. 389-93Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Our aim was to determine whether the aldosterone synthase (CYP11B2) -344 C/T polymorphism was associated with the blood pressure (BP)-lowering response to antihypertensive treatment. METHODS: Patients with mild-to-moderate primary hypertension and left ventricular hypertrophy were randomized in a double-blind study to receive treatment with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan (n = 43), or the beta1-adrenergic receptor blocker atenolol (n = 43). The aldosterone synthase (CYP11B2) -344 C/T polymorphism was analyzed using solid-phase minisequencing and related to BP reduction after 3 months treatment. Serum aldosterone levels were measured. RESULTS: After 3 months treatment the mean reductions in BP were similar for both treatment groups. When assessing the systolic BP reduction in the irbesartan group, patients with the TT variant had a more pronounced reduction (-21 +/- 19 SD mm Hg, n = 17) than both the TC (-14 +/- 18 mm Hg, n= 18) and CC (0 +/- 17 mm Hg, n = 8) genotypes (P = .04). There was no association between this polymorphism and the diastolic BP response. The -344 C/T polymorphism was not associated with the BP response to atenolol. Nor was it related to the baseline serum aldosterone level. CONCLUSIONS: The aldosterone synthase -344 C/T polymorphism was related to the BP-lowering response in hypertensive patients treated with the AT1-receptor antagonist irbesartan.

Keywords
Adrenergic beta-Antagonists/*therapeutic use, Aldosterone/blood, Aldosterone Synthase/*genetics, Antihypertensive Agents/*therapeutic use, Atenolol/*therapeutic use, Base Sequence/genetics, Biphenyl Compounds/*therapeutic use, Blood Pressure, Comparative Study, Cytosine, Double-Blind Method, Female, Humans, Hypertension/blood/*drug therapy/*genetics/physiopathology, Hypertrophy; Left Ventricular/drug therapy, Male, Middle Aged, Polymorphism; Genetic, Receptor; Angiotensin; Type 1, Receptors; Angiotensin/antagonists & inhibitors, Research Support; Non-U.S. Gov't, Tetrazoles/*therapeutic use, Thymine, Treatment Outcome
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-73165 (URN)10.1016/S0895-7061(02)02256-2 (DOI)12022239 (PubMedID)
Available from: 2005-06-01 Created: 2005-06-01 Last updated: 2017-12-14Bibliographically approved
Hallberg, P., Karlsson, J., Kurland, L., Lind, L., Kahan, T., Malmqvist, K., . . . Melhus, H. (2002). The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. Journal of Hypertension, 20(10), 2089-2093
Open this publication in new window or tab >>The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial
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2002 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 20, no 10, p. 2089-2093Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT(1)) receptor antagonists, losartan and irbesartan. Single nucleotide polymorphisms in the CYP2C9 gene result in the expression of three important variants, CYP2C9*1(wild-type), CYP2C9*2 and CYP2C9*3, the last two exhibiting reduced catalytic activity compared with the wild-type. The CYP2C9 genotype is known to determine sensitivity to and dose requirements for both warfarin and phenytoin, and also the rate of metabolism of losartan. However, its influence on clinical response to treatment with the AT(1) receptor antagonist, irbesartan, has not been investigated. OBJECTIVE: To determine whether the CYP2C9genotype influences the blood pressure-decreasing response to antihypertensive treatment with irbesartan. DESIGN AND METHODS: One hundred and two patients with essential hypertension and left ventricular hypertrophy were allocated randomly to groups to receive double-blind treatment with either irbesartan (n = 49) or the beta(1)-adrenergic receptor blocker, atenolol ( n= 53). Blood pressure was measured before and after 12 weeks of treatment. genotyping was performed using solid-phase minisequencing. RESULTS: The diastolic blood pressure (DBP) response differed in relation to the CYP2C9 genotype in patients given irbesartan: the reduction in patients with genotype CYP2C9*1/CYP2C9*1 (n = 33) was 7.5% and that with CYP2C9*1/CYP2C9*2 (n = 12) was 14.4% ( P= 0.036). A similar trend was seen for systolic blood pressure. In contrast, no relation was seen between the CYP2C9 genotype and blood pressure response to atenolol, a drug not metabolized via CYP2C9. CONCLUSIONS: The CYP2C9 genotype seems to predict the DBP response to irbesartan, but not to atenolol, in patients with essential hypertension.

Keywords
Adult, Aged, Antihypertensive Agents/administration & dosage/*therapeutic use, Aryl Hydrocarbon Hydroxylases/*drug effects/*genetics, Atenolol/administration & dosage/therapeutic use, Biphenyl Compounds/administration & dosage/*therapeutic use, Blood Pressure/*drug effects/*genetics, Comparative Study, Diastole/drug effects/genetics, Dose-Response Relationship; Drug, Double-Blind Method, Drug Evaluation, Female, Genotype, Humans, Hypertension/drug therapy/physiopathology, Hypertrophy; Left Ventricular/drug therapy/physiopathology, Male, Middle Aged, Predictive Value of Tests, Randomized Controlled Trials, Research Support; Non-U.S. Gov't, Sweden, Systole/drug effects/genetics, Tetrazoles/administration & dosage/*therapeutic use, Treatment Outcome
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-73219 (URN)12359989 (PubMedID)
Available from: 2005-06-02 Created: 2005-06-02 Last updated: 2017-12-14Bibliographically approved
Kurland, L., Melhus, H., Karlsson, J., Kahan, T., Malmqvist, K., Öhman, K. P., . . . Lind, L. (2001). Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients. Journal of Hypertension, 19(10), 1783-1787
Open this publication in new window or tab >>Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients
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2001 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 19, no 10, p. 1783-1787Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.

Keywords
Adrenergic beta-Antagonists/therapeutic use, Antihypertensive Agents/*therapeutic use, Atenolol/therapeutic use, Biphenyl Compounds/*therapeutic use, Blood Pressure/*drug effects, Double-Blind Method, Female, Forecasting, Humans, Hypertension/*drug therapy/*genetics, Male, Middle Aged, Peptidyl-Dipeptidase A/*genetics, Polymorphism; Genetic/*physiology, Receptor; Angiotensin; Type 1, Receptors; Angiotensin/*antagonists & inhibitors, Research Support; Non-U.S. Gov't, Tetrazoles/*therapeutic use, Treatment Outcome
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-73122 (URN)11593098 (PubMedID)
Available from: 2008-06-17 Created: 2008-06-17 Last updated: 2017-12-14Bibliographically approved
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