A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response

Liljedahl, UlrikaUppsala universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Uppsala University, Uppsala, Sweden (author)

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.

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
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

Karlsson, JuliaUppsala universitet,Institutionen för medicinska vetenskaper,Osteoporos,Department of Medical Sciences, Uppsala University, Uppsala, Sweden (author)
Melhus, HåkanUppsala universitet,Institutionen för medicinska vetenskaper,Osteoporos,Department of Medical Sciences, Uppsala University, Uppsala, Sweden(Swepub:uu)hakamelh (author)
Kurland, Lisa,1960-Uppsala universitet,Institutionen för medicinska vetenskaper,Akut- och internmedicin,Department of Medical Sciences, Uppsala University, Uppsala, Sweden(Swepub:oru)lkd (author)
Lindersson, MarieDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden(Swepub:uu)marielin (author)
Kahan, ThomasKarolinska Institutet (author)
Nyström, Fredrik,1963-Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Internmedicin,EMT-endo(Swepub:liu)freny92 (author)
Lind, LarsUppsala universitet,Institutionen för medicinska vetenskaper,Akut- och internmedicin,Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Astra Zeneca R&D, Mölndal, Sweden(Swepub:uu)larslind (author)
Syvänen, Ann-ChristineUppsala universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Uppsala University, Uppsala, Sweden(Swepub:uu)anncsyva (author)
Uppsala universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

In:Pharmacogenetics: Ovid Technologies (Wolters Kluwer Health)13:1, s. 7-170960-314X1473-561X

By the author/editor: Liljedahl, Ulrik ...; Karlsson, Julia; Melhus, Håkan; Kurland, Lisa, 1 ...; Lindersson, Mari ...; Kahan, Thomas; show more...; Nyström, Fredrik ...; Lind, Lars; Syvänen, Ann-Chr ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

By the university: Uppsala University; Örebro University; Karolinska Institutet; Linköping University

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