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dc.contributor.authorBraenne Ingrid
dc.contributor.authorZeng Lingyao
dc.contributor.authorWillenborg Christina
dc.contributor.authorTragante Vinicius
dc.contributor.authorKessler Thorsten
dc.contributor.authorWiller Cristen J
dc.contributor.authorLaakso Markku
dc.contributor.authorWallentin Lars
dc.contributor.authorFranks Paul W
dc.contributor.authorSalomaa Veikko
dc.contributor.authorDehghan Abbas
dc.contributor.authorMeitinger Thomas
dc.contributor.authorSamani Nilesh J
dc.contributor.authorAsselbergs Folkert W
dc.contributor.authorErdmann Jeanette
dc.contributor.authorSchunkert Heribert
dc.contributor.authorCARDIoGRAM Consortium
dc.contributor.authorCARDIoGRAMplusC4D Consortium
dc.date.accessioned2018-01-12T11:32:23Z
dc.date.available2018-01-12T11:32:23Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/5169
dc.description.abstractGlatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10−12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10−10 and 2.21 × 10−6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.en
dc.language.isoENen
dc.publisherPublic Library of Science (PLoS)en
dc.relation.ispartofseriesPLOS ONEen
dc.relation.urihttp://dx.doi.org/10.1371/journal.pone.0182999en
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.titleGenomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risken
dc.description.versionpublished versionen
dc.contributor.departmentSchool of Medicine / Clinical Medicineen
uef.solecris.id49391678en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7-HEALTH-2013-INNOVATION-1/601456/EU/Exploitation of genomic variants affecting coronary artery disease and stroke risk for therapeutic intervention/CVGENES-AT-TARGETen
dc.relation.doi10.1371/journal.pone.0182999en
dc.description.reviewstatuspeerRevieweden
dc.relation.articlenumbere0182999en
dc.relation.issn1932-6203en
dc.relation.issue8en
dc.relation.volume12en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


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