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Individual and cumulative effect of type 2 diabetes genetic susceptibility variants on risk of coronary heart disease
- Source :
- Diabetologia. 54(9)
- Publication Year :
- 2011
-
Abstract
- Type 2 diabetes is a major risk factor for CHD. We hypothesised that diabetes genetic susceptibility variants might be associated with increased CHD risk.We examined the individual and cumulative effect of 38 common genetic variants previously reported to be associated with type 2 diabetes on risk of incident CHD in 20,467 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk Study who had been free of CHD at baseline.During a mean follow-up of 10.7 years, 2,190 participants had a CHD event. Two individual variants next to the TSPAN8 (HR 1.07, 95% CI 1.00-1.14) and the CDKN2A/B region (1.11, 1.04-1.17) were significantly associated with increased CHD risk. A genetic score based on the 38 diabetes variants was significantly associated with an increased risk of CHD (1.08, 1.01-1.14 per score tertile). Adjustment for prevalent and incident diabetes attenuated the association of the TSPAN8 variant (1.06, 0.99-1.13) and the genetic score (1.05, 0.99-1.12 per score tertile) with CHD risk, but not that of the CDKN2A/B variant (1.11, 1.05-1.18). Addition of the genetic score did not improve risk discrimination based on clinical risk factors.The increased risk of CHD observed with genetic susceptibility to type 2 diabetes was at least partly mediated by its diabetes-predisposing effect and was not useful for clinical risk discrimination. The potential role of pathways associated with the variant CDKN2A/B in linking diabetes and CHD needs further exploration.
- Subjects :
- Adult
Male
medicine.medical_specialty
Tetraspanins
Endocrinology, Diabetes and Metabolism
Single-nucleotide polymorphism
Type 2 diabetes
Bioinformatics
Risk Factors
Internal medicine
Diabetes mellitus
Internal Medicine
Genetic predisposition
Medicine
Humans
Genetic Predisposition to Disease
cardiovascular diseases
Longitudinal Studies
Prospective Studies
Prospective cohort study
Cumulative effect
Cyclin-Dependent Kinase Inhibitor p16
Aged
Cyclin-Dependent Kinase Inhibitor p15
business.industry
Incidence
Genetic Variation
Middle Aged
medicine.disease
Coronary heart disease
United Kingdom
Diabetes Mellitus, Type 2
Cardiovascular Diseases
Cardiology
Female
business
Chd risk
Follow-Up Studies
Subjects
Details
- ISSN :
- 14320428
- Volume :
- 54
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Diabetologia
- Accession number :
- edsair.doi.dedup.....40acc6e12191a99b276ccba083cae5a2