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01.06.2014 | Article

A serum 25-hydroxyvitamin D concentration-associated genetic variant in DHCR7 interacts with type 2 diabetes status to influence subclinical atherosclerosis (measured by carotid intima–media thickness)

verfasst von: Rona J. Strawbridge, Anna Deleskog, Olga McLeod, Lasse Folkersen, Maryam Kavousi, Karl Gertow, Damiano Baldassarre, Fabrizio Veglia, Karin Leander, Bruna Gigante, Jussi Kauhanen, Rainer Rauramaa, Andries J. Smit, Elmo Mannarino, Philippe Giral, Abbas Dehghan, Albert Hofman, Oscar H. Franco, Steve E. Humphries, Elena Tremoli, Ulf de Faire, Sven Gustafsson, Claes-Göran Östensson, Per Eriksson, John Öhrvik, Anders Hamsten

Erschienen in: Diabetologia | Ausgabe 6/2014

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Abstract

Aims/hypothesis

The findings of studies investigating whether or not low serum 25-hydroxyvitamin D [25(OH)D] concentration promotes development of atherosclerosis have been contradictory. The present study employed a Mendelian randomisation approach and carotid artery intima–media thickness (cIMT), a surrogate marker of coronary artery disease, to address this question.

Methods

The multicentre, longitudinal Carotid Intima–Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population (IMPROVE) cohort study, which enrolled individuals with at least three cardiovascular risk factors and no history or symptoms of cardiovascular disease, was used for the present investigation. Participants underwent carotid ultrasound examination at baseline and at months 15 and 30. Six single nucleotide polymorphisms (SNPs) associated with serum 25(OH)D concentration in genome-wide association studies were identified and genotyped in 3,418 individuals, of whom 929 had type 2 diabetes.

Results

SNPs in the genes encoding vitamin D binding protein (GC; rs2282679 and rs7041) and 7-dehydrocholesterol reductase/NAD synthetase-1 (DHCR7; rs12785878 and rs3829251) were negatively associated with 25(OH)D levels. Effect sizes and significance of associations between SNPs and 25(OH)D levels differed between individuals with and without type 2 diabetes, although no significant interactions were observed. A SNP in DHCR7 interacted with type 2 diabetes to significantly influence progression of cIMT measures independent of 25(OH)D levels and established risk factors. Expression analysis demonstrated that this SNP modulates DHCR7 mRNA levels in aortic adventitia.

Conclusions/interpretation

SNPs in GC and DHCR7 were associated with serum levels of 25(OH)D, but only rs3829251 (DHCR7) influenced progression of subclinical atherosclerosis, as measured by cIMT, in a manner dependent on type 2 diabetes status but independent of 25(OH)D levels.

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Titel: A serum 25-hydroxyvitamin D concentration-associated genetic variant in DHCR7 interacts with type 2 diabetes status to influence subclinical atherosclerosis (measured by carotid intima–media thickness)
verfasst von: Rona J. Strawbridge
Anna Deleskog
Olga McLeod
Lasse Folkersen
Maryam Kavousi
Karl Gertow
Damiano Baldassarre
Fabrizio Veglia
Karin Leander
Bruna Gigante
Jussi Kauhanen
Rainer Rauramaa
Andries J. Smit
Elmo Mannarino
Philippe Giral
Abbas Dehghan
Albert Hofman
Oscar H. Franco
Steve E. Humphries
Elena Tremoli
Ulf de Faire
Sven Gustafsson
Claes-Göran Östensson
Per Eriksson
John Öhrvik
Anders Hamsten
Publikationsdatum: 01.06.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 6/2014
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-014-3215-y

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