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)

Autor: Steve E. Humphries, Karl Gertow, Bruna Gigante, Per Eriksson, Oscar H. Franco, Elmo Mannarino, Olga McLeod, Ulf de Faire, Rona J. Strawbridge, Philippe Giral, John Öhrvik, Andries J. Smit, Anders Hamsten, Lasse Folkersen, Jussi Kauhanen, Claes Göran Östensson, Elena Tremoli, Rainer Rauramaa, Albert Hofman, Fabrizio Veglia, Abbas Dehghan, Sven A. Gustafsson, Karin Leander, Damiano Baldassarre, Maryam Kavousi, Anna Deleskog
Přispěvatelé: Epidemiology, Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP)
Rok vydání: 2014
Předmět:
VITAMIN-D DEFICIENCY
Oxidoreductases Acting on CH-CH Group Donors
medicine.medical_specialty
D INSUFFICIENCY
Genotype
Interaction
Endocrinology
Diabetes and Metabolism
PARATHYROID-HORMONE
Parathyroid hormone
NUTRITION EXAMINATION SURVEY
Type 2 diabetes
Polymorphism
Single Nucleotide
vitamin D deficiency
Coronary artery disease
SDG 3 - Good Health and Well-being
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
Vitamin D and neurology
3RD NATIONAL-HEALTH
Humans
cardiovascular diseases
Myocardial infarction
Subclinical atherosclerosis
Carotid intima-media thickness
Vitamin D
GENOME-WIDE ASSOCIATION
ARTERY INTIMA
Genetic variant
Aged
business.industry
Middle Aged
medicine.disease
Endocrinology
Diabetes Mellitus
Type 2
Intima-media thickness
MYOCARDIAL-INFARCTION
CARDIOVASCULAR-DISEASE
cardiovascular system
RISK-FACTORS
business
Genome-Wide Association Study
Zdroj: Diabetologia, 57(6), 1159-1172. Springer-Verlag
Diabetologia, 57(6), 1159-1172. SPRINGER
ISSN: 1432-0428
0012-186X
Popis: 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.
Databáze: OpenAIRE
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