Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment

• BACKGROUND: Our aim was to determine whether the change in left ventricular (LV) mass in response to antihypertensive treatment could be predicted by multivariate analysis of single nucleotide polymorphisms (SNPs) in candidate genes reflecting pathways likely to be involved in blood pressure control. METHODS: Patients with mild to moderate primary hypertension and LV hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n = 48) or the beta1 adrenoreceptor blocker atenolol (n = 49). A microarray-based minisequencing system was used for genotyping 74 SNPs in 25 genes. These genotypes were related to the change in LV mass index by echocardiography, after 12 weeks treatment as monotherapy, using stepwise multiple regression analysis. RESULTS: The blood pressure reductions were similar and significant in both treatment groups. Two SNPs in two separate genes (the angiotensinogen T1198C polymorphism, corresponding to the M235T variant and the apolipoprotein B G10108A polymorphism) for those treated with irbesartan, and the adrenoreceptor alpha2A A1817G for those treated with atenolol, significantly predicted the change in LV mass. The predictive power of these SNPs was independent of the degree of blood pressure reduction. CONCLUSION: SNPs in the angiotensinogen, apolipoprotein B, and the alpha2 adrenoreceptor gene predicted the change in LV mass during antihypertensive therapy. These results illustrate the potential of using microarray-based technology for SNP genotyping in predicting individual drug responses.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Nyckelord

Adrenergic beta-Antagonists/therapeutic use

Angiotensin II Type 1 Receptor Blockers/therapeutic use

Angiotensinogen/genetics

Antihypertensive Agents/*therapeutic use

Apolipoproteins B/genetics

Atenolol/therapeutic use

Biphenyl Compounds/therapeutic use

Blood Pressure/*genetics

Double-Blind Method

Echocardiography

Female

Genotype

Humans

Hypertension/complications/*drug therapy/*genetics

Hypertrophy; Left Ventricular/etiology/*ultrasonography

Male

Middle Aged

Multivariate Analysis

Oligonucleotide Array Sequence Analysis

Pharmacogenetics

Polymorphism; Single Nucleotide

Predictive Value of Tests

Receptors; Adrenergic; beta-2/genetics

Research Support; Non-U.S. Gov't

Tetrazoles/therapeutic use

MEDICINE

MEDICIN

Publikations- och innehållstyp

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