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)
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- 作者：Rona J. Strawbridge (1)
Anna Deleskog (1) (2)
Olga McLeod (1)
Lasse Folkersen (1)
Maryam Kavousi (3) (4)
Karl Gertow (1)
Damiano Baldassarre (5)
Fabrizio Veglia (5)
Karin Leander (6)
Bruna Gigante (6)
Jussi Kauhanen (7)
Rainer Rauramaa (8)
Andries J. Smit (4) (9)
Elmo Mannarino (10)
Philippe Giral (11)
Abbas Dehghan (3) (4)
Albert Hofman (3) (4)
Oscar H. Franco (3) (4)
Steve E. Humphries (12)
Elena Tremoli (5)
Ulf de Faire (6)
Sven Gustafsson (2)
Claes-G?ran ?stensson (2)
Per Eriksson (1)
John ?hrvik (1)
Anders Hamsten (1) - 关键词：Carotid intima–media thickness ; Genetic variant ; Interaction ; Subclinical atherosclerosis ; Type 2 diabetes ; Vitamin D
- 刊名：Diabetologia
- 出版年：2014
- 出版时间：June 2014
- 年：2014
- 卷：57
- 期：6
- 页码：1159-1172
- 全文大小：
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Anna Deleskog (1) (2)
Olga McLeod (1)
Lasse Folkersen (1)
Maryam Kavousi (3) (4)
Karl Gertow (1)
Damiano Baldassarre (5)
Fabrizio Veglia (5)
Karin Leander (6)
Bruna Gigante (6)
Jussi Kauhanen (7)
Rainer Rauramaa (8)
Andries J. Smit (4) (9)
Elmo Mannarino (10)
Philippe Giral (11)
Abbas Dehghan (3) (4)
Albert Hofman (3) (4)
Oscar H. Franco (3) (4)
Steve E. Humphries (12)
Elena Tremoli (5)
Ulf de Faire (6)
Sven Gustafsson (2)
Claes-G?ran ?stensson (2)
Per Eriksson (1)
John ?hrvik (1)
Anders Hamsten (1)
1. Atherosclerosis Research Unit, Centre for Molecular Medicine, Building L8:03, Karolinska University Hospital Solna, 17176, Stockholm, Sweden
2. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
3. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
4. Netherlands Genomics Initiative-Sponsored Netherlands Consortium for Healthy Ageing, Rotterdam, The Netherlands
5. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano & Centro Cardiologico Monzino, IRCCS, Milan, Italy
6. Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
7. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
8. Foundation for Research in Health, Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland
9. Department of Medicine, University Medical Center Groningen, Groningen, The Netherlands
10. Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
11. Assistance Publique–H?pitaux de Paris; Service Endocrinologie–Metabolisme, Groupe H?pitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, Paris, France
12. Centre for Cardiovascular Genetics, University College London, London, UK - ISSN：1432-0428
文摘
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.