Microarray Technology for Genotyping in Pharmacogenetics

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Liljedahl, Ulrika,1976-Uppsala universitet,Institutionen för medicinska vetenskaper (författare)

Microarray Technology for Genotyping in Pharmacogenetics

BokEngelska2004

Förlag, utgivningsår, omfång ...

Uppsala :Acta Universitatis Upsaliensis,2004
69 s.
electronicrdacarrier

Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:uu-4222
ISBN:9155459374
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4222URI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:vet swepub-contenttype
Ämneskategori:dok swepub-publicationtype

Serie

Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,0282-7476 ;1342

Anmärkningar

The studies in this thesis describe the development of a microarray based minisequencing system and its application to highly parallel genotyping of single nucleotide polymorphisms. The technical developments included identification of a three-dimensional microarray surface coating with high binding capacity for oligonucleotides modified with amino groups as the most optimal one for the system. The system was also established for multiplexed, reproducible quantitative analysis of SNP alleles both on the level of DNA and RNA. The sensitivity of the system to distinguish SNP alleles present as a minority in a mixed sample was found to be 1-6%.The microarray based minisequencing system was applied in a pharmacogenetic study on antihypertensive drug response. A panel of 74 SNPs located in candidate genes related to blood pressure regulation were genotyped in DNA samples from hypertensive patients that had been treated with the antihypertensive drugs irbesartan or atenolol. Multiple regression analysis of the genotype data against the reduction in blood pressure identified genotype combinations of four to five SNPs that explain 44-56% of the reduction in blood pressure in the two treatment groups. The genotypes of two individual SNPs in the angiotensinogen (AGT) gene and a SNP in the low density lipoprotein receptor (LDLR) gene appeared to be associated to reduced blood pressure after treatment with atenolol, while a SNP in the apolipoprotein B (APOB) gene was associated to blood pressure reduction after irbesartan treatment. The genotype of one SNP in the adrenergic alpha-2A-receptor gene (ADRA2A) was related to the reduction in left ventricular mass following atenolol treatment while the genotypes of two SNPs, one in the APOB gene and one in the AGT gene were related to the reduction in left ventricular mass in the patients treated with irbesartan.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
Molecular medicine
microarray
genotyping
pharmacogenetics
molecular medicine
single nucleotide polymorphism
hypertension
Molekylärmedicin
Molecular medicine (genetics and pathology)
Molekylär medicin (genetik och patologi)

Biuppslag (personer, institutioner, konferenser, titlar ...)

Syvänen, Ann-Christine (preses)
Grant, Denis,ProfessorDepartment of Pharmacology, Institute for Drug Research, University of Toronto, Toronto (opponent)
Uppsala universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

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Av författaren/redakt...: Liljedahl, Ulrik ...; Syvänen, Ann-Chr ...; Grant, Denis, Pr ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Medicinsk geneti ...

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Av lärosätet: Uppsala universitet

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