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)

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 TremoliUlf De Faire, Sven Gustafsson, Claes Göran Östensson, Per Eriksson, John Öhrvik, Anders Hamsten

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1159-1172
Number of pages14
JournalDiabetologia
Volume57
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Carotid Intima-Media Thickness
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Atherosclerosis
Serum
Carotid Arteries
Vitamin D-Binding Protein
Adventitia
Genome-Wide Association Study
Random Allocation
Blood Vessels
25-hydroxyvitamin D
Coronary Artery Disease
Cohort Studies
Cardiovascular Diseases
Biomarkers
History
Messenger RNA
Population
Genes

Keywords

  • Carotid intima-media thickness
  • Genetic variant
  • Interaction
  • Subclinical atherosclerosis
  • Type 2 diabetes
  • Vitamin D

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

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

In: Diabetologia, Vol. 57, No. 6, 2014, p. 1159-1172.

Research output: Contribution to journalArticle

Strawbridge, RJ, Deleskog, A, McLeod, O, Folkersen, L, Kavousi, M, Gertow, K, Baldassarre, D, Veglia, F, Leander, K, Gigante, B, Kauhanen, J, Rauramaa, R, Smit, AJ, Mannarino, E, Giral, P, Dehghan, A, Hofman, A, Franco, OH, Humphries, SE, Tremoli, E, De Faire, U, Gustafsson, S, Östensson, CG, Eriksson, P, Öhrvik, J & Hamsten, A 2014, '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)', Diabetologia, vol. 57, no. 6, pp. 1159-1172. https://doi.org/10.1007/s00125-014-3215-y
Strawbridge, Rona J. ; Deleskog, Anna ; McLeod, Olga ; Folkersen, Lasse ; Kavousi, Maryam ; Gertow, Karl ; Baldassarre, Damiano ; Veglia, Fabrizio ; Leander, Karin ; Gigante, Bruna ; Kauhanen, Jussi ; Rauramaa, Rainer ; Smit, Andries J. ; Mannarino, Elmo ; Giral, Philippe ; Dehghan, Abbas ; Hofman, Albert ; Franco, Oscar H. ; Humphries, Steve E. ; Tremoli, Elena ; De Faire, Ulf ; Gustafsson, Sven ; Östensson, Claes Göran ; Eriksson, Per ; Öhrvik, John ; Hamsten, Anders. / 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). In: Diabetologia. 2014 ; Vol. 57, No. 6. pp. 1159-1172.
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T1 - 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)

AU - Strawbridge, Rona J.

AU - Deleskog, Anna

AU - McLeod, Olga

AU - Folkersen, Lasse

AU - Kavousi, Maryam

AU - Gertow, Karl

AU - Baldassarre, Damiano

AU - Veglia, Fabrizio

AU - Leander, Karin

AU - Gigante, Bruna

AU - Kauhanen, Jussi

AU - Rauramaa, Rainer

AU - Smit, Andries J.

AU - Mannarino, Elmo

AU - Giral, Philippe

AU - Dehghan, Abbas

AU - Hofman, Albert

AU - Franco, Oscar H.

AU - Humphries, Steve E.

AU - Tremoli, Elena

AU - De Faire, Ulf

AU - Gustafsson, Sven

AU - Östensson, Claes Göran

AU - Eriksson, Per

AU - Öhrvik, John

AU - Hamsten, Anders

PY - 2014

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KW - Carotid intima-media thickness

KW - Genetic variant

KW - Interaction

KW - Subclinical atherosclerosis

KW - Type 2 diabetes

KW - Vitamin D

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