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A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response

Liljedahl, Ulrika (author)
Uppsala universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Karlsson, Julia (author)
Uppsala universitet,Institutionen för medicinska vetenskaper,Osteoporos,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Melhus, Håkan (author)
Uppsala universitet,Institutionen för medicinska vetenskaper,Osteoporos,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Kurland, Lisa, 1960- (author)
Uppsala universitet,Institutionen för medicinska vetenskaper,Akut- och internmedicin,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Lindersson, Marie (author)
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Kahan, Thomas (author)
Karolinska Institutet
Nyström, Fredrik, 1963- (author)
Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Internmedicin,EMT-endo
Lind, Lars (author)
Uppsala universitet,Institutionen för medicinska vetenskaper,Akut- och internmedicin,Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Astra Zeneca R&D, Mölndal, Sweden
Syvänen, Ann-Christine (author)
Uppsala universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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 (creator_code:org_t)
Ovid Technologies (Wolters Kluwer Health), 2003
2003
English.
In: Pharmacogenetics. - : Ovid Technologies (Wolters Kluwer Health). - 0960-314X .- 1473-561X. ; 13:1, s. 7-17
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • We aimed to develop a microarray genotyping system for multiplex analysis of a panel of single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in blood pressure regulation, and to apply this system in a pilot study demonstrating its feasibility in the pharmacogenetics of hypertension. A panel of 74 SNPs in 25 genes involved in blood pressure regulation was selected from the SNP databases, and genotyped in DNA samples of 97 hypertensive patients. The patients had been randomized to double-blind treatment with either the angiotensin II type 1 receptor blocker irbesartan or the beta 1-adrenergic receptor blocker atenolol. Genotyping was performed using a microarray based DNA polymerase assisted 'minisequencing' single nucleotide primer extension assay with fluorescence detection. The observed genotypes were related to the blood pressure reduction using stepwise multiple regression analysis. The allele frequencies of the selected SNPs were determined in the Swedish population. The established microarray-based genotyping system was validated and allowed unequivocal multiplex genotyping of the panel of 74 SNPs in every patient. Almost 7200 SNP genotypes were generated in the study. Profiles of four or five SNP-genotypes that may be useful as predictors of blood pressure reduction after antihypertensive treatment were identified. Our results highlight the potential of microarray-based technology for SNP genotyping in pharmacogenetics.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

Adrenergic beta-Antagonists/therapeutic use
Antihypertensive Agents/*therapeutic use
DNA Primers/genetics
Databases; Genetic
Double-Blind Method
Female
Gene Expression/*drug effects
Gene Expression Profiling
Gene Frequency/*drug effects
Genotype
Humans
Hypertension/*drug therapy/genetics
Male
Middle Aged
Oligonucleotide Array Sequence Analysis/*methods
Pharmacogenetics/*methods
Polymorphism; Single Nucleotide/*genetics
Random Allocation
Receptor; Angiotensin; Type 1
Receptors; Angiotensin/antagonists & inhibitors/metabolism
Research Support; Non-U.S. Gov't
MEDICINE
MEDICIN

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ref (subject category)
art (subject category)

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