RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation
Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Univ Glasgow, Inst Mental Hlth & Wellbeing, Mental Hlth & Wellbeing, Glasgow, Lanark, Scotland.;Univ Glasgow, Dept Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland..
Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.ORCID-id: 0000-0001-8081-428X
Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
Vise andre og tillknytning
2017 (engelsk)Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 266, s. 196-204Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.

Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.

Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.

Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.

sted, utgiver, år, opplag, sider
2017. Vol. 266, s. 196-204
Emneord [en]
Proinsulin, Atherosclerosis, Intima-media-thickness, Single nucleotide polymorphisms, Genetic variants, Mendelian randomisation
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-341363DOI: 10.1016/j.atherosclerosis.2017.09.031ISI: 000414069700027PubMedID: 29040868OAI: oai:DiVA.org:uu-341363DiVA, id: diva2:1181397
Forskningsfinansiär
Swedish Research Council, 8691 09533 2012-1397 2015-03657Swedish Heart Lung Foundation, 20120197 20140543EU, European Research CouncilKnut and Alice Wallenberg FoundationSwedish Foundation for Strategic Research Stockholm County Council, 592229EU, FP7, Seventh Framework Programme, IMI/115006Swedish National Infrastructure for Computing (SNIC), b2011036Tilgjengelig fra: 2018-02-08 Laget: 2018-02-08 Sist oppdatert: 2018-02-08bibliografisk kontrollert

Open Access i DiVA

fulltext(1015 kB)7 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 1015 kBChecksum SHA-512
15bb59cc764d2a25d04e0c7f8492cfef8418304bb3b44c66b50aa963a877bab45952fda8ca8e4e633e85336ee28565c7e8bd5c44df9873a3acf232cc8abc8716
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Søk i DiVA

Av forfatter/redaktør
den Hoed, MarcelGustafsson, StefanLannfelt, LarsLind, LarsSennblad, BengtSyvänen, Ann-ChristineZethelius, Björn
Av organisasjonen
I samme tidsskrift
Atherosclerosis

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 7 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 19 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf